Miracle-dz/UniFAR-FTUs huggingface dataset:
Conditional survival and hazards of death for peripheral T-cell lymphomas

Typically, peripheral T-cell lymphoma (PTCLs) prognosis is estimated using overall survival before treatment. However, these estimates cannot show how prognosis evolves with the changing hazard rate over time. Patients (n = 650) with newly diagnosed PTCLs were enrolled retrospectively. After a median follow-up of 5.4 years, angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) and NK/T cell lymphoma had initially lower 3-year conditional overall survival (COS3; i.e., the 3-year conditional overall survival was defined as the probability of surviving an additional 3 years) and higher hazards of death (26–44.3%). However, after 2 years, the COS3 increased and the death risk decreased over time, whereas anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma constantly had a lower risk over time (0–19.5%). For patients with complete remission after initial treatment, prognosis varied by histological subtypes, with PTCL, NOS having a negative impact. Our data suggested that the risk stratification using the International Prognostic Index might not accurately predict the COS3 for survivors of PTCLs. The COS3 provided time-dependent prognostic information for PTCLs, representing a possible surrogate prognosis indicator for long-term survivors after systemic chemotherapy.
Phenotypic diversity and history of the Congo Basin populations: Equatorial Guinea, Bantu Speaking Central Africans and African Pygmies

Abstract Background African Pygmy Populations (APP) are believed to be one of the first groups of the Congo Basin rainforest peoples to separate from the rest of modern humanity. The arrival of Bantu speaking agriculturalists from 5,000 BP led to the formation of a large number of ethnic complexes in Central Africa and the Atlantic coastal area, mainly due to a one-way flow of pygmy women. There are now only a few small contingents of African Pygmy population groups who are mixed or who have almost disappeared as a result of migratory flows from Cameroon. Aims We analysed the adult phenotypic diversity of 9 populations (17 groups of both sexes) of the Congo basin and Bioko Island, which were anthropometrically characterised in 1948. The phenotypic clusters that we detected, which we interpret as likely mixing of local Pygmy populations and Bantus, may be useful as references for future studies, particularly genetics. Subjects and methods The matrix of inter-distances between populations was generated, using the 21 variables, with the Euclidean distance between the mean vectors relating to the standardised variables. When the UPGMA (Unweighted Pair Group Method with Arithmetic Mean) was used separately in men and women, the phylogenetic trees showed a clear separation between populations. Results The body measurements that most effectively distinguished the groups are linear dimensions and the width of the hips and mean thoracic circumference. In this study, the cephalo-facial dimensions were of little value in identifying the groups. Conclusions The samples of Equatorial Guinea show a major inter-group overlap, and considerable intra-group variations. There are also notable differences amongst African Pygmy populations in terms of height, but not in body proportions.
Root and canopy traits and adaptability genes explain drought tolerance responses in winter wheat

Bread wheat (Triticum aestivum L) is one of the three main staple crops worldwide contributing 20% calories in the human diet. Drought stress is the main factor limiting yields and threatening food security, with climate change resulting in more frequent and intense drought. Developing drought-tolerant wheat cultivars is a promising way forward. The use of holistic approaches that include high-throughput phenotyping and genetic markers in selection could help in accelerating genetic gains. Fifty advanced breeding lines were selected from the CIMMYT Turkey winter wheat breeding program and studied under irrigated and semiarid conditions in two years. High-throughput phenotyping was done for wheat crown root traits and canopy senescence dynamics using vegetation indices (green area using RGB images and Normalized Difference Vegetation Index using spectral reflectance). In addition, genotyping by KASP markers for adaptability genes was done. Overall, under semiarid conditions yield reduced by 3.09 t ha-1 (-46.8%) compared to irrigated conditions. Genotypes responded differently under drought stress and genotypes 39 (VORONA/HD24-12//GUN/7/VEE#8//…/8/ALTAY), 18 (BiII98) and 29 (NIKIFOR//KROSHKA) were the most drought tolerant. Root traits including shallow nodal root angle under irrigated conditions and root number per shoot under semiarid conditions were correlated with increased grain yield. RGB based vegetation index measuring canopy green area at anthesis was better correlated with GY than NDVI was with GY under drought. The markers for five established functional genes (PRR73.A1 –flowering time, TEF-7A –grain size and weight, TaCwi.4A - yield under drought, Dreb1- drought tolerance, and ISBW11.GY.QTL.CANDIDATE- grain yield) were associated with different drought-tolerance traits in this experiment. We conclude that–genotypes 39, 18 and 29 could be used for drought tolerance breeding. The trait combinations of canopy green area at anthesis, and root number per shoot along with key drought adaptability makers (TaCwi.4A and Dreb1) could be used in screening drought tolerance wheat breeding lines.
The impact of force magnitude on the first and second maxillary molars in cervical headgear therapy

Summary Aim To study the effect of force magnitude on the maxillary first and second molars in cervical headgear (CHG) therapy. Material and methods In this controlled clinical trial, patients (n = 40) were treated with CHG with a light (L, 300 g, n = 22) or a heavy force (H, 500 g, n = 18) magnitude. The subjects were asked to wear CHG for 10 hours a day for 10 months. The outer bow of the CHG facebow was lifted up for 10–20 degrees and the inner bow was expanded 3–4 mm. Adherence to instructions and force magnitude were monitored using an electronic module (Smartgear, Swissorthodontics, Switzerland). Panoramic and lateral radiographs before (T1) and after treatment (T2) were analysed using a Romexis Cephalometric module (Planmeca, Finland) focussing on the angular, sagittal, and vertical positions of the permanent first and second molars. Results According to the cephalometric analysis of the maxillary first and second molars, distal tipping occurred during T1–T2 in the H group (P = 0.010 and 0.000, respectively), and the change was greater in the H group compared to the L group (P = 0.045 and 0.019, respectively). Based on the panoramic analysis, tipping occurred in the distal direction during therapy in the H group in the second molars compared to the midline or condylar line (P = 0.001 and 0.001; P = 0.008 and 0.003 on the right and left, respectively). Conclusion With heavy force magnitude, the maxillary first and second molars can tilt more easily in the distal direction even if the CHG was used less. Distal tipping of the molar can be considered to be a side effect of CHG therapy.
Fatty acid oxidation participates in resistance to nutrient-depleted environments in the insect stages of Trypanosoma cruzi

Trypanosoma cruzi, the parasite causing Chagas disease, is a digenetic flagellated protist that infects mammals (including humans) and reduviid insect vectors. Therefore, T. cruzi must colonize different niches in order to complete its life cycle in both hosts. This fact determines the need of adaptations to face challenging environmental cues. The primary environmental challenge, particularly in the insect stages, is poor nutrient availability. In this regard, it is well known that T. cruzi has a flexible metabolism able to rapidly switch from carbohydrates (mainly glucose) to amino acids (mostly proline) consumption. Also established has been the capability of T. cruzi to use glucose and amino acids to support the differentiation process occurring in the insect, from replicative non-infective epimastigotes to non-replicative infective metacyclic trypomastigotes. However, little is known about the possibilities of using externally available and internally stored fatty acids as resources to survive in nutrient-poor environments, and to sustain metacyclogenesis. In this study, we revisit the metabolic fate of fatty acid breakdown in T. cruzi. Herein, we show that during parasite proliferation, the glucose concentration in the medium can regulate the fatty acid metabolism. At the stationary phase, the parasites fully oxidize fatty acids. [U-14C]-palmitate can be taken up from the medium, leading to CO2 production. Additionally, we show that electrons are fed directly to oxidative phosphorylation, and acetyl-CoA is supplied to the tricarboxylic acid (TCA) cycle, which can be used to feed anabolic pathways such as the de novo biosynthesis of fatty acids. Finally, we show as well that the inhibition of fatty acids mobilization into the mitochondrion diminishes the survival to severe starvation, and impairs metacyclogenesis.
Mosquito Net Ownership, Utilization, and Preferences among Mobile and Migrant Populations Sleeping in Forests and Farms in Central Vietnam: A Cross-Sectional Study

ABSTRACT Strengthening vector control measures among mobile and migrant populations (MMPs) is crucial to malaria elimination, particularly in areas with multidrug-resistant malaria. Although a global priority, providing access and ensuring high coverage of available tools such as long-lasting insecticidal nets (LLINs) among these vulnerable groups remains a significant challenge. We assessed mosquito net ownership, utilization, and preference among individuals who slept in a forest and/or on a farm against those residing only in village “home” settings in a priority malaria elimination area of Vietnam. Proportions of respondents owning bed nets were similar among forest, farm, and home sleeping sites, ranging between 96% and 98%. The proportion of respondents owning hammock nets was higher for the forest group (92%), whereas ownership of hammocks in general was significantly lower for the home group (55%). Most respondents (97%) preferred to bring hammock nets to their remote sleeping site, whereas a smaller proportion (25%) also considered bed nets as an option. Respondent preferences included thick hammock nets with zippers (53%), hammocks with a flip cover (17%), and thin hammock nets with zippers (15%), with none choosing polyethylene (hard) LLINs. Although there is high coverage and access to nets for this high-priority MMP group, there was a noted gap between coverage and net use, potentially undermining the effectiveness of net-related interventions that could impact malaria prevention and elimination efforts in Vietnam. The design and material of nets are important factors for user preferences that appear to drive net use.
A Phase Ib/II Study of Pepinemab in Combination with Avelumab in Advanced Non–Small Cell Lung Cancer

Purpose: The CLASSICAL-Lung clinical trial tested the combination of pepinemab, an IgG4 humanized mAb targeting semaphorin 4D, with the PD-L1 inhibitor avelumab to assess the effects of coupling increased T-cell infiltration and reversal of immune suppression via pepinemab with sustained T-cell activation via checkpoint inhibition. Patients and Methods: This phase Ib/II, single-arm study was designed to evaluate the safety, tolerability, and efficacy of pepinemab in combination with avelumab in 62 patients with advanced non–small cell lung cancer (NSCLC), including immunotherapy-naïve (ION) patients and patients whose tumors progressed following anti-PD-1/L1 monotherapy (IOF). The main objectives were to evaluate safety/tolerability, establish a recommended phase 2 dose (RP2D), obtain a preliminary evaluation of antitumor activity, and investigate candidate biomarker activity. Results: The combination was well tolerated with no major safety signals identified. Pepinemab, 10 mg/kg with avelumab, 10 mg/kg, every 2 weeks, was selected as the RP2D. Among 21 evaluable ION patients, 5 patients experienced partial responses (PR), 4 patients evidenced clinical benefit ≥1 year, and the disease control rate (DCR) was 81%. Notably, overall response rate with the combination therapy was higher than previously reported for single-agent avelumab in the PD-L1-negative/low population. Among 29 evaluable IOF patients, the combination resulted in a DCR of 59%, including 2 PR and 7 patients with durable clinical benefit of ≥23 weeks. Biomarker analysis of biopsies demonstrated increased CD8 T-cell density correlating with RECIST response criteria. Conclusions: The combination of pepinemab with avelumab was well tolerated in NSCLC and showed signs of antitumor activity in immunotherapy-resistant and PD-L1-negative/low tumors.
Mood Disorders and Outcomes of COVID-19 Hospitalizations.

OBJECTIVE The authors sought to characterize the association between prior mood disorder diagnosis and hospital outcomes among individuals admitted with COVID-19 to six Eastern Massachusetts hospitals. METHODS A retrospective cohort was drawn from the electronic health records of two academic medical centers and four community hospitals between February 15 and May 24, 2020. Associations between history of mood disorder and in-hospital mortality and hospital discharge home were examined using regression models among any hospitalized patients with positive tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RESULTS Among 2,988 admitted individuals, 717 (24.0%) had a prior mood disorder diagnosis. In Cox regression models adjusted for age, sex, and hospital site, presence of a mood disorder prior to admission was associated with greater in-hospital mortality risk beyond hospital day 12 (crude hazard ratio=2.156, 95% CI=1.540, 3.020; fully adjusted hazard ratio=1.540, 95% CI=1.054, 2.250). A mood disorder diagnosis was also associated with greater likelihood of discharge to a skilled nursing facility or other rehabilitation facility rather than home (crude odds ratio=2.035, 95% CI=1.661, 2.493; fully adjusted odds ratio=1.504, 95% CI=1.132, 1.999). CONCLUSIONS Hospitalized individuals with a history of mood disorder may be at risk for greater COVID-19 morbidity and mortality and are at increased risk of need for postacute care. Further studies should investigate the mechanism by which these disorders may confer elevated risk.
Inhibition of STAT3 prevents bone metastatic progression of prostate cancer in vivo

Prostate cancer (PC) metastasizes to the skeleton forming predominantly sclerotic lesions, and there is currently no cure for bone metastatic disease. The transcription factor signal transducer and activator of transcription 3 (STAT3) is implicated as a metastatic driver, but its potential as therapeutic target in bone metastasis has not been investigated. In this study, we evaluated for the first time a STAT3 inhibitor, Napabucasin, as a therapeutic option for bone metastatic PC.
Rollout of COVID-19 Vaccination in India: A SWOT Analysis

Objective: This study aimed to identify the strengths, weaknesses, opportunities, and threats (SWOT) in the rollout of the COVID-19 vaccination campaign in India. Methods: The internal and external attributes affecting the vaccination rollout identifed by reviewing the scientific literature, government guidelines, and press statements, along with media reports, were categorized into the SWOT matrix. Results: The existing immunization program, indigenous vaccine production, setting up of the National Expert Group on Vaccine Administration for COVID-19, updated guidelines, and training followed by dry runs were identified as strengths. The weaknesses identified in the program were knowledge gap about vaccines, apprehensions, lack of temperature loggers and vaccine vial monitors, space contraints in health care set up, demand supply gap, and digital divide. The experience of conducting the general elections, intersectoral coordination forged during the pandemic response, Information Technology platform, and vaccine eagerness present opportunities to strengthen the program. The emergence of virus variants, commercial interests, laxity in COVID-19 appropriate behavior, and receding wave of the pandemic can pose significant threats to the implementation of the vaccination campaign. Conclusion: The study identified factors that can aid designing effective measures and countermeasures for the COVID-19 vaccination rollout. This SWOT analysis is relevant to low- and middle-income countries planning to implement the COVID-19 vaccination in the near future.
Salt stress enhances early symbiotic gene expression in Medicago truncatula and induces a stress-specific set of rhizobium-responsive genes.

Salt stress is a major agricultural concern inhibiting not only plant growth but also the symbiotic association between legume roots and the soil bacteria rhizobia. This symbiotic association is initiated by a molecular dialogue between the two partners, leading to the activation of a signaling cascade in the legume host and ultimately the formation of nitrogen-fixing root nodules. Here we show that a moderate salt stress increases the responsiveness of early symbiotic genes in Medicago truncatula to its symbiotic partner, Sinorhizobium meliloti, while conversely, inoculation with S. meliloti counteracts salt-regulated gene expression, restoring one-third to control levels. Our analysis of Early Nodulin 11 shows that salt-induced expression is dynamic, Nod-factor dependent, and requires the ionic, but not the osmotic, component of salt. We demonstrate that salt stimulation of rhizobium-induced gene expression requires NSP2, which functions as a node to integrate the abiotic and biotic signals. In addition, our work reveals that inoculation with Sinorhizobium meliloti succinoglycan mutants also hyperinduces ENOD11 expression in the presence or absence of salt, suggesting a possible link between rhizobial exopolysaccharide and the plant response to salt stress. Finally, we identify an accessory set of genes that are induced by rhizobium only under conditions of salt stress and have not been previously identified as being nodulation-related genes. Our data suggests that interplay of core nodulation genes with different accessory sets, specific for different abiotic conditions, function to establish the symbiosis. Together, our findings reveal a complex and dynamic interaction between plant, microbe, and environment.
Muscle size of individual hip extensors in sprint runners: Its relation to spatiotemporal variables and sprint velocity during maximal velocity sprinting

Hip extensor muscle size is related to sprint running performance. However, the mechanisms underlying this relationship remain unclear. To gain insights into this issue, the present study examined the relationships between the individual hip extensor sizes, spatiotemporal variables (step frequency and length, and their determinants), and sprint velocity during maximal velocity sprinting. Magnetic resonance images of the hip and right thigh were obtained from 26 male sprinters to determine the volumes of the gluteus maximus, individual hamstrings and adductors, and gracilis. Muscle volumes were normalized to their respective body mass and recorded as relative muscle volumes. The sprinters performed a 100-m sprint with their maximal effort. Their sprint motions were recorded using cameras to calculate the mean sprint velocity and the spatiotemporal variables at 50–60 m interval. The sprint velocity was significantly correlated with the relative volume of the semitendinosus (r = 0.497, P = 0.010), but not with the volumes of the other examined muscles. The relative volume of semitendinosus significantly correlated with the stance distance (r = 0.414, P = 0.036) and the stance distance adjusted by the stance time (r = 0.490, P = 0.011). Moreover, there were significant correlations between the stance distance and step length (r = 0.592, P = 0.001), and between the step length and sprint velocity (r = 0.509, P = 0.008). These results suggest that the semitendinosus contributes to attaining long stance distance and thereby high sprint velocity during maximal velocity sprinting.
Associations of neighborhood physical and crime environments with obesity-related outcomes in Jamaica

Objective To examine whether proximity and density of public open spaces, public parks, street connectivity, and serious and violent crimes were associated with Body Mass Index (BMI) and Waist Circumference (WC) within and across levels of urbanicity, sex and socioeconomic status (SES) in Jamaica, a small island developing state (SIDS). Methods Secondary analysis was conducted using data from the Jamaica Health and Lifestyle Survey 2008 (JHLS II). All respondents were geocoded to area of residence in Enumeration Districts (EDs). Intraclass correlation coefficients (ICCs) were derived and multilevel mixed effects regression models applied to 2529 participants nested within 101 EDs from all 14 parishes in Jamaica. Results There was significant clustering across neighborhoods for mean BMI (ICC = 4.16%) and mean WC (ICC = 4.42%). In fully adjusted models statistically significant associations included: increased mean BMI among men, with increased intersection density/ km2 (β = 0.02; 95% CI = 1.96 x10-3, 0.04, p = 0.032); increased mean WC among urban residents with increased crimes/km2/yr (β = 0.09; 95% CI = 0.03, 0.16, p<0.01) and among persons in the middle class, with further distance away from public parks (β = 0.30; 95% CI = 0.08, 0.53, p<0.01). Conclusions Neighborhood physical and crime environments were associated with obesity-related outcomes in Jamaica. Policymakers in SIDS such as Jamaica should also note the important differences by urbanicity, sex and SES in prevention efforts designed to stem the growing obesity epidemic.
In Vitro and In Vivo Activities, Absorption, Tissue Distribution, and Excretion of OBP-4, a Potential Anti-Clostridioides difficile Agent

Clostridioides difficile infection (CDI) is considered a major concern of the health care system globally, with an increasing need for alternative therapies. OBP-4, a new oxazolidinone-fluoroquinolone hybrid with excellent in vitro activities and good safety, shows promising features as an antibacterial agent. ABSTRACT Clostridioides difficile infection (CDI) is considered a major concern of the health care system globally, with an increasing need for alternative therapies. OBP-4, a new oxazolidinone-fluoroquinolone hybrid with excellent in vitro activities and good safety, shows promising features as an antibacterial agent. Here, we further evaluated the in vitro and in vivo activities of OBP-4 against C. difficile and its absorption (A), distribution (D), and excretion (E) profiles in rats. In vitro assays indicated that OBP-4 was active against all tested C. difficile strains, with MICs ranging from 0.25 to 1 mg/liter. In addition, OBP-4 showed complete inhibition of spore formation at 0.5× MIC. In the mouse model of CDI, 5-day oral treatment with OBP-4 provided complete protection from death and CDI recurrence in infected mice. However, cadazolid (CZD) and vancomycin (VAN) showed less protection of infected mice than did OBP-4 in terms of diarrhea and weight loss, especially VAN. Subsequently, ADE investigations of OBP-4 with a reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method showed extremely low systemic exposure and predominantly fecal excretion, resulting in a high local concentration of OBP-4 in the intestinal tract—the site of CDI. These results demonstrated that OBP-4 possesses good activity against C. difficile and favorable ADE characteristics for oral treatment of CDI, which support further development of OBP-4 as a potential anti-CDI agent.