Genetic continuity of Indo-Iranian speakers since the Iron Age in southern Central Asia

Since prehistoric times, southern Central Asia has been at the crossroads of the movement of people, culture, and goods. Today, the Central Asian populations are divided into two cultural and linguistic groups: the Indo-Iranian and the Turko-Mongolian groups. Previous genetic studies unveiled that migrations from East Asia contributed to the spread of Turko-Mongolian populations in Central Asia and the partial replacement of the Indo-Iranian populations. However, little is known about the origin of the latters. To shed light on this, we compare the genetic data on two current-day Indo-Iranian populations — Yaghnobis and Tajiks — with genome-wide data from published ancient individuals. The present Indo-Iranian populations from Central Asia display a strong genetic continuity with Iron Age samples from Turkmenistan and Tajikistan. We model Yaghnobis as a mixture of 93% Iron Age individual from Turkmenistan and 7% from Baikal. For the Tajiks, we observe a higher Baikal ancestry and an additional admixture event with a South Asian population. Our results, therefore, suggest that in addition to a complex history, Central Asia shows a remarkable genetic continuity since the Iron Age, with only limited gene flow.

Correlation of Mismatch Repair Deficiency with Clinicopathological Features and Programmed Death-Ligand 1 Expression in Thyroid Carcinoma

Background Mutations in DNA mismatch repair (MMR) genes associated with thyroid carcinoma (TC) have rarely been reported, especially in East Asian populations. Methods We examined tumor tissue from a cohort of 241 patients diagnosed with TC between 2008 and 2020. MMR proteins were detected using tissue microarray-based immunohistochemistry in order to identify MMR-protein-deficient (MMR-D) and MMR-protein-intact (MMR-I) tumors. We retrospectively summarized the clinicopathologic characteristics of patients with MMR-D TC, measured the expression of PD-L1, and recorded overall survival (OS) and other clinical outcomes. Results In our cohort, there were 18 (7.5%) MMR-D (MLH1, MSH2, MSH6, and PMS2) patients, including 12 with papillary TC (PTC) (6.7%), 2 with poorly differentiated TC (PDTC) (4.7%), and 4 with anaplastic TC (ATC) (22.2%). Half of them (9/18) showed a specific deletion in MSH6, and 6 of them also carried variants in the MSH6 and PMS2 gene. Survival was significantly better in patients with MMR-D ATC than in those with MMR-I tumors (p=0.033). Four of the 18 MMR-D patients (22%) were found to be PD-L1 positive. Their OS was much shorter than that of PD-L1-negative patients. Conclusions MMR-D and PD-L1 positivity appear to be associated with clinicopathological characteristics and prognosis in TC. The results indicate that MMR status may have important prognostic significance in TC. Therefore, immune checkpoint inhibitors that target the PD-1/PD-L1 pathway may be a treatment option for TCs.

Development and validation of a circulating microRNA panel for the early detection of breast cancer

Background Mammography is widely used for breast cancer screening but suffers from a high false-positive rate. Here, we perform the largest comprehensive, multi-center study to date involving diverse ethnic groups, for the identification of circulating miRNAs for breast cancer screening. Methods This study had a discovery phase (n = 289) and two validation phases (n = 374 and n = 379). Quantitative PCR profiling of 324 miRNAs was performed on serum samples from breast cancer (all stages) and healthy subjects to identify miRNA biomarkers. Two-fold cross-validation was used for building and optimising breast cancer-associated miRNA panels. An optimal panel was validated in cohorts with Caucasian and Asian samples. Diagnostic ability was evaluated using area under the curve (AUC) analysis. Results The study identified and validated 30 miRNAs dysregulated in breast cancer. An optimised eight-miRNA panel showed consistent performance in all cohorts and was successfully validated with AUC, accuracy, sensitivity, and specificity of 0.915, 82.3%, 72.2% and 91.5%, respectively. The prediction model detected breast cancer in both Caucasian and Asian populations with AUCs ranging from 0.880 to 0.973, including pre-malignant lesions (stage 0; AUC of 0.831) and early-stage (stages I–II) cancers (AUC of 0.916). Conclusions Our panel can potentially be used for breast cancer screening, in conjunction with mammography.

New-Onset Ulcerative Colitis in a Young Caucasian Woman with Unclassified Arteritis

Takayasu arteritis is a rare disease mostly found in Asian populations. Cases have been reported in patients with inflammatory bowel disease, suggesting possible genetic linkage. The objective of this clinical case report is to highlight a rare finding of arteritis signs and symptoms in a 32-year-old Caucasian woman (likely early that it did not yet meet classification for official diagnosis as Takayasu arteritis) who subsequently was diagnosed with ulcerative colitis a few months later. The patient presented to the hospital with throbbing neck pain and tenderness around the area of her right carotid artery distribution, nonspecific visual changes, and bilateral upper extremity paresthesia, with significant findings of 50-69% right carotid artery stenosis on a recent outpatient carotid Doppler ultrasound. Based on additional laboratory, clinical, and advanced imaging findings at the hospital, a diagnosis of arteritis not yet classifiable as Takayasu arteritis was made, and the patient was treated with corticosteroids. Unfortunately, she developed bradycardia that was later attributed to the corticosteroid regimen and the medication was discontinued. By follow-up in the clinic, the patient’s carotidynia improved, but now, she reported a three-month history of bloody stools. Colonoscopy and pathology findings were consistent with ulcerative colitis, and the patient was started on mesalamine. The association of inflammatory bowel disease and Takayasu arteritis should not be overlooked, as future treatment methods and early, continuous surveillance may be critical in improving quality of life and avoiding serious complications.

Mitochondrial DNA Footprints from Western Eurasia in Modern Mongolia

Mongolia is located in a strategic position at the eastern edge of the Eurasian Steppe. Nomadic populations moved across this wide area for millennia before developing more sedentary communities, extended empires, and complex trading networks, which connected western Eurasia and eastern Asia until the late Medieval period. We provided a fine-grained portrait of the mitochondrial DNA (mtDNA) variation observed in present-day Mongolians and capable of revealing gene flows and other demographic processes that took place in Inner Asia, as well as in western Eurasia. The analyses of a novel dataset (N = 2,420) of mtDNAs highlighted a clear matrilineal differentiation within the country due to a mixture of haplotypes with eastern Asian (EAs) and western Eurasian (WEu) origins, which were differentially lost and preserved. In a wider genetic context, the prevalent EAs contribution, larger in eastern and central Mongolian regions, revealed continuous connections with neighboring Asian populations until recent times, as attested by the geographically restricted haplotype-sharing likely facilitated by the Genghis Khan’s so-called Pax Mongolica. The genetic history beyond the WEu haplogroups, notably detectable on both sides of Mongolia, was more difficult to explain. For this reason, we moved to the analysis of entire mitogenomes (N = 147). Although it was not completely possible to identify specific lineages that evolved in situ, two major changes in the effective (female) population size were reconstructed. The more recent one, which began during the late Pleistocene glacial period and became steeper in the early Holocene, was probably the outcome of demographic events connected to western Eurasia. The Neolithic growth could be easily explained by the diffusion of dairy pastoralism, as already proposed, while the late glacial increase indicates, for the first time, a genetic connection with western Eurasian refuges, as supported by the unusual high frequency and internal sub-structure in Mongolia of haplogroup H1, a well-known post-glacial marker in Europe. Bronze Age events, without a significant demographic impact, might explain the age of some mtDNA haplogroups. Finally, a diachronic comparison with available ancient mtDNAs made it possible to link six mitochondrial lineages of present-day Mongolians to the timeframe and geographic path of the Silk Route.

A genetic history of migration, diversification, and admixture in Asia

L.L. Cavalli-Sforza spearheaded early efforts to study the genetic history of humans, recognizing the importance of sampling diverse populations worldwide. He supported research on human evolutionary genetics in Asia, with research on human dispersal into Asia and genetic distances between present-day East Asians in the late 20th century. Since then, great strides have been made in understanding the genetic history of humans in Asia, through large-scale genomic sequencing of present-day humans and targeted sequencing of DNA from ancient humans. In this review, I survey the genetic prehistory of humans in Asia, based on research using sequence data from humans who lived in Asia as early as 45,000 years ago. Genetic studies comparing present-day Australasians and Asians show that they likely derived from a single dispersal out of Africa, rapidly differentiating into three main lineages: one that persists partially in South Asia, one that is primarily found today in Australasia, and one that is widely represented across Siberia, East Asia, and Southeast Asia. Studies of ancient DNA from human remains in Asia dating from as far back as 45,000 years has greatly increased our understanding of the population dynamics leading to the current Asian populations. Based on "Jin L, Underhill PA, Doctor V, Davis RW, Shen P, Cavalli-Sforza LL, Oefner PJ. Distribution of haplotypes from a chromosome 21 region distinguishes multiple prehistoric human migrations. Proc Natl Acad Sci U S A. 1999;96(7):3796-3800”.

Chronic Kidney Disease in a Large National Human Immunodeficiency Virus Treatment Program

Introduction: Tenofovir disoproxil fumarate (TDF) is associated with a risk of chronic kidney disease (CKD), especially when used with protease inhibitors or in Asian populations. Data from the Thai national health insurance system were used to assess the incidence of CKD in patients receiving antiretroviral therapy (ART) in real-world practice. Materials and methods We analyzed data from patients who initiated one of the following first-line ART regimens: (i) zidovudine+lamivudine+nevirapine (AZT+3TC+NVP); (ii) zidovudine+lamivudine+efavirenz (AZT+3TC+EFV); (iii) tenofovir+lamivudine+nevirapine (TDF+3TC+NVP); (iv) tenofovir+lamivudine/emtricitabine+efavirenz (TDF+3TC/FTC+EFV); and (v) tenofovir+lamivudine+lopinavir/ritonavir (TDF+3TC+LPV/r). CKD was defined as glomerular filtration rate <60 mL/min/1.73 m2 for >3 months, or a confirmed 2010 WHO diagnosis (ICD-10 code N183, N184, or N185). Death competing risks survival regression models were used for the analysis. Results Among 27,313 participants, median age 36.8 years, body mass index 20.4 kg/m2, and absolute CD4 cell count 146 cells/mm3, followed for a median 2.3 years, 245 patients (0.9%) were diagnosed CKD (incidence 3.2 per 1,000 patient-years of follow-up; 95% confidence interval [CI] 2.8-3.6). Compared with patients receiving AZT+3TC+NVP, the risk of CKD measured by adjusted sub-distribution hazard ratio (aSHR) was higher in patients on TDF+3TC+LPV/r (6.5, 95% CI 3.9-11.1), on TDF+3TC+NVP (3.8, 95% CI 2.3-6.0) and on TDF+3TC/FTC+EFV (1.6, 95% CI 1.2-2.3). Among patients receiving TDF, compared with those receiving TDF+3TC/FTC+EFV, the risk was higher on TDF+3TC+LPV/r (4.0, 95%CI 2.3-6.8) on TDF+3TC+NVP (2.3, 95%CI 1.4-3.6) . Conclusions This real-world study suggest that the role of TDF in increasing the risk of CKD, especially when combined with LPV/r or NVP.

Transient neonatal hyperpigmentation of the proximal nail fold in a Chinese infant: a case report

Cutaneous alterations are common in neonates and usually occur in the first few days of life. Most of these are transient and benign, appearing as physiological responses to birth. Skin pigmentation disorders are considered transitory dermatoses of newborn infants. Nail pigmentation manifests as asymptomatic brown to bluish-black skin pigmentation over the fingers and toes in newborns. Hyperpigmentation of the distal phalanx of both hands and feet is commonly found in dark-skinned newborns, but it is rare in fair-skinned newborns and East Asian populations. We herein describe a Chinese infant with transient neonatal hyperpigmentation of the proximal nail fold.

A Comparison of IgG Index and Oligoclonal Band in the Cerebrospinal Fluid for Differentiating between RRMS and NMOSD

As the oligoclonal band in the cerebrospinal fluid (CSF-OCB) in predicting relapsing-remitting multiple sclerosis (RRMS) is less sensitive in Asian populations than that in westerners, it remains elusive whether the IgG index could serve as an alternative. The purpose of this study was to compare these two methods of differentiating between RRMS and neuromyelitis optica spectrum disorder (NMOSD) in Chinese patients. A total of 171 patients (81 RRMS and 90 NMOSD) were retrospectively recruited, of whom 82 (56 RRMS and 26 NMOSD) received the CSF-OCB testing additionally. When the onset age was ≤38.5 years, IgG index with the threshold of 0.67 had a significant agreement (к = 0.4, p < 0.001) with the diagnosis while CSF-OCB failed to discriminate (к = 0.1, p = 0.578). However, when the onset age was >38.5 years, both IgG index with the threshold of 0.8 and CSF-OCB were moderately consistent with the diagnosis (both к > 0.4, p < 0.05). In total, our optimized algorithm had the sensitivity, specificity, and predictive accuracy of 0.778, slightly outperforming the CSF-OCB model. Accordingly, a combination of the onset age and IgG index could serve as an alternative to CSF-OCB for differentiating between RRMS and NMOSD in Chinese patients.

Examine the Association between Metabolic Syndrome and Frailty in an Older Asian Population

Background: There has been evidence that metabolic syndrome (MetS) may increase the risk of frailty. However, there is limited evidence on this association in Asian populations. Aims: This study aims to identify the association between MetS and frailty in older people in Vietnam. Methods: This is a cross-sectional analysis of a dataset obtained from an observational study on frailty and sarcopenia in patients aged &ge;60 at a geriatric hospital in Vietnam. Frailty was defined by the frailty phenotype. Participants were defined as having MetS if they had &ge;3 out of 5 criteria from the definition of the National Cholesterol Education Program (NCEP) Adults Treatment Panel (ATP) III. Multiple logistic regression models were performed to estimate the risk of having frailty in patients with MetS. Results: There were 669 participants (mean age 71, 60.2% female), 62.3% had MetS and 39.0% was frail. The prevalence of frailty was 42.2% in participants with MetS, 33.7% in participants without MetS (p=0.029). On logistic regression models, MetS was associated with increased likelihood of being frail (adjusted OR 1.52, 95%CI 1.01-2.28), allowing for age, sex, education, nutritional status, history of hospitalisation and chronic diseases. Conclusion: There was a significant association between MetS and frailty in this population. Further longitudinal studies are required to confirm this association.