bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Approach for Therapeutic Drug Monitoring of Valproic Acid Using FT-IR Spectroscopy and Nonlinear Support Vector Regression
Authors: El Orche Aimen , Cheikh Amine , Johnson Joel B , Elhamdaoui Omar , Jawhari Samira , El Abbes Faouzi Moulay , Cherrah Yahia , Mbarki Mohamed , Bouatia Mustapha 
Published: November 2022

Abstract

Background
Recent technological progress has bolstered efforts to bring personalized medicine from theory into clinical practice. However, progress in areas such as therapeutic drug monitoring (TDM) has remained somewhat stagnant. In drugs with well-known dose-response relationships, TDM can enhance patient outcomes and reduce health care costs. Traditional monitoring methods such as chromatography-based or immunoassay techniques are limited by their higher costs and slow turnaround times, making them unsuitable for real-time or onsite analysis.

Objective
In this work, we propose the use of a fast, direct, and simple approach using Fourier transform infrared spectroscopy (FT-IR) combined with chemometric techniques for the therapeutic monitoring of valproic acid (VPA).

Method
In this context, a database of FT-IR spectra was constructed from human plasma samples containing various concentrations of VPA; these samples were characterized by the reference method (immunoassay technique) to determine the VPA contents. The FT-IR spectra were processed by two chemometric regression methods: partial least-squares regression (PLS) and support vector regression (SVR).

Results
The results provide good evidence for the effectiveness of the combination of FT-IR spectroscopy and SVR modeling for estimating VPA in human plasma. SVR models showed better predictive abilities than PLS models in terms of root-mean-square error of calibration and prediction RMSEC, RMSEP, R2Cal, R2Pred, and residual predictive deviation (RPD).

Conclusions
This analytical tool offers potential for real-time TDM in the clinical setting.

Highlights
FTIR spectroscopy was evaluated for the first time to predict VPA in human plasma for TDM. Two regressions were evaluated to predict VPA in human plasma, and the best-performing model was obtained using nonlinear SVR.
Interindividual differences in crop foraging behavior of chimpanzees (Pan troglodytes schweinfurthii) at a forest–agriculture interface
Authors: Couturier Chloé , Lacroux Camille , Okimat John Paul , Asalu Edward , Krief Sabrina 
Published: November 2022

AbstractThe expansion of agriculture in equatorial areas is fragmenting and reducing wildlife habitats. For primates, it also increases opportunities to consume crops as high-energy resources, exacerbates conflicts with farmers, and increases exposure to diseases and agrochemicals at the edge of protected areas. In species with sex differences in ranging behavior, individual exposure to such opportunities and threats may vary by sex. Chimpanzees show a great feeding flexibility and are territorial species with varied ranging patterns according to site, sex, or individuals. Within a community whose territory is crossed by a high-traffic road and partially bordered by maize gardens, we tested hypotheses of interindividual differences in access to crops based on age, sex, ranging behavior, and kinship. By analyzing the presence of Sebitoli chimpanzees (Pan troglodytes schweinfurthii, Kibale National Park, Uganda) on video clips from 16 camera traps, we estimated the individual dispersion range across the community’s territory and the crop foraging frequency along maize gardens over 16 months. While all age and sex classes were represented at the forest–garden interface, large intrasex differences were observed: some mature males and females were not observed to participate. The crop foraging frequency of adult females in maize gardens was significantly correlated with the location of their ranging areas. Related individuals revealed similar range patterns within the forest territory without sharing crop foraging habits. However, social learning and energy and risks–benefits trade-offs as potential drivers of crop consumption are not excluded.
Senescent endometrial stromal cells transmit reactive oxygen species to the trophoblast-like cells and impair spreading of blastocyst-like spheroids
Authors: Deryabin P I , Ivanova J S , Borodkina A V 
Published: November 2022

Abstract
Successful implantation requires a fine-tuned dialog between the invading embryo and the maternal endometrium. Recently, we discovered that premature senescence of endometrial stromal cells (EnSC) might mediate improper decidual transformation of endometrial tissue and impair endometrial–blastocyst interaction. Here, we show that senescent EnSC are characterized by elevated intracellular reactive oxygen species (ROS) levels that originate from mitochondrial dysfunction and insufficient antioxidant defense. Decidualization of senescent EnSC is defective and is accompanied by the elevated intracellular and mitochondrial ROS levels. Antioxidant defense during decidualization is significantly less efficient in senescent EnSC compared to healthy ones. Senescent EnSC secrete increased amounts of ROS into the extracellular space. Elevated ROS released by senescent EnSC shift the redox balance and induce DNA damage in the neighboring trophoblast-like cells. In an in vitro implantation model, we observed impaired spreading of blastocyst-like spheroids into a monolayer of decidualizing senescent EnSC, which could be compensated by pretreatment of the senescent cells with the antioxidant, Tempol. Hence, we propose a possible mechanism that might be responsible, at least in part, for the defective embryo implantation realized via ROS transmitting from senescent EnSC to trophoblast cells. Such transmission results in the accumulation of ROS and subsequent DNA damage in trophoblastic cells, which might lead to improper migration and invasion of an embryo. In light of these findings, the application of antioxidants prior to implantation might be a promising strategy to improve implantation efficiency.
Single-cell transcriptomic Atlas of mouse cochlear aging
Authors: Sun Guoqiang , Zheng Yandong , Fu Xiaolong , Zhang Weiqi , Ren Jie , Ma Shuai , Sun Shuhui , He Xiaojuan , Wang Qiaoran , Ji Zhejun , Cheng Fang , Yan Kaowen , Liu Ziyi , Izpisua Belmonte Juan Carlos , Qu Jing , Wang Si , Chai Renjie , Liu Guang-Hui 
Published: November 2022

Abstract
Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-related transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.
TCDD alters essential transcriptional regulators of osteogenic differentiation in multipotent mesenchymal stem cells
Authors: Watson AtLee T D , Carmona Baez Aldo , Jima Dereje , Reif David , Ding Jun , Roberts Reade , Kullman Seth W 
Published: November 2022

AbstractDifferentiation of multipotent mesenchymal stem cells (MSCs) into bone-forming osteoblasts requires strict coordination of transcriptional pathways. Aryl hydrocarbon receptor ligands, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), have been shown to alter osteoblast differentiation in vitro and bone formation in multiple developmental in vivo models. The goal of the present study was to establish a global transcriptomic landscape during early, intermediate, and apical stages of osteogenic differentiation in vitro in response to TCDD exposure. Human bone-derived mesenchymal stem cells (hBMSCs) were cultured in growth media (GM), osteogenic differentiation media (ODM), or ODM containing 10 nM TCDD (ODM + TCDD), thus enabling a comparison of the transcriptomic profiles of undifferentiated, differentiated, and differentiated-TCDD-exposed hBMSCs, respectively. In this test system, exposure to TCDD attenuated the differentiation of hBMSCs into osteoblasts as evidenced by reduced alkaline phosphatase activity and mineralization. At various timepoints, we observed altered expression of genes that play a role in the Wnt, fibroblast growth factor, bone morphogenetic protein/transforming growth factor beta developmental pathways, as well as pathways related to extracellular matrix organization and deposition. Reconstruction of gene regulatory networks with the interactive dynamic regulatory event miner (iDREM) analysis revealed modulation of transcription factors (TFs) including POLR3G, NR4A1, RDBP, GTF2B, POU2F2, and ZEB1, which may putatively influence osteoblast differentiation and the requisite deposition and mineralization of bone extracellular matrix. We demonstrate that the combination of RNA-Seq data in conjunction with the iDREM regulatory model captures the transcriptional dynamics underlying MSC differentiation under different conditions in vitro. Model predictions are consistent with existing knowledge and provide a new tool to identify novel pathways and TFs that may facilitate a better understanding of the osteoblast differentiation process, perturbation by exogenous agents, and potential intervention strategies targeting those specific pathways.
Association of Endometriosis and Severe Maternal Morbidity
Authors: Lafleur Nahantara , Wei Shu Qin , Bilodeau-Bertrand Marianne , Auger Nathalie 
Published: November 2022

OBJECTIVE:
To evaluate the association between endometriosis and risk of severe maternal morbidity (SMM).

METHODS:
We conducted a population-based retrospective cohort study of 2,412,823 deliveries at hospitals in Quebec, Canada, between 1989 and 2019. The exposure was surgically confirmed endometriosis. Patients were classified as having active endometriosis during pregnancy, inactive endometriosis during pregnancy, a diagnosis of endometriosis postpregnancy, or no endometriosis. The outcome was SMM, including by a range of life-threatening maternal conditions during pregnancy or up to 42 days postdelivery. We computed rates of SMM and used log binomial regression to assess the association with endometriosis (risk ratio [RR]; 95% CI), adjusted for maternal characteristics.

RESULTS:
Severe maternal morbidity occurred in 46.2 of 1,000 patients with endometriosis, compared with 30.7 of 1,000 patients without endometriosis. Relative to no exposure, endometriosis was associated with 1.43 times the risk of SMM (95% CI 1.36–1.51). Patients with endometriosis that was active during pregnancy had a greater risk of SMM (RR 1.93; 95% CI 1.76–2.11). Active endometriosis was associated with the risk of severe preeclampsia and eclampsia, severe hemorrhage, hysterectomy, cardiac complications, embolism, shock, sepsis, and intensive care unit admission. Inactive endometriosis was less strongly associated with these outcomes.

CONCLUSION:
Pregnant patients with endometriosis, especially active endometriosis, have a greater risk of SMM and may benefit from closer follow-up to prevent severe complications of pregnancy.
Fused Clitoral Hood Presenting as a Periclitoral Mass
Authors: Maybury Edward K. , Recio Fernando O. , Ahmad Sarfraz , McKenzie Nathalie D. 
Published: November 2022

BACKGROUND:
Periclitoral masses are seldom reported. One cause is a congenitally fused clitoral prepuce (or clitoral hood).

CASE:
A patient was referred to our gynecologic oncology practice with a suspicious periclitoral mass for evaluation of possible malignancy. The clitoral hood was, in fact, fused such that the glans was completely covered. Surgical excision of the distal prepuce (or clitoral hood) expelled trapped sebaceous material and revealed a normal-appearing glans clitoris. Clitoral hood reconstruction restored the patient's external genitalia to normal anatomy.

CONCLUSION:
Fused clitoral prepuce causing trapped sebaceous material can mimic an expanding periclitoral mass and should be considered in the differential diagnosis.
Impact of Scalene Muscle Botulinum Toxin Injection With and Without Surgery in Neurogenic Thoracic Outlet Syndrome
Authors: Fereydooni Arash , Ho Vy T. , Olson Emily Miller , Dyrek Paige , Harris Taylor , Kussman Andrea , Roh Eugene , Lee Jason T. 
Published: November 2022

Objective:
Scalene blocks are part of both the diagnostic and treatment algorithm for patients presenting with symptoms of neurogenic thoracic outlet syndrome (nTOS). However, there is a paucity of data on the utility of scalene botulinum toxin injection (BTI) before surgical decompression. We sought to determine the impact of BTI with and without surgery at a multidisciplinary referral center.

Design:
Retrospective cohort study.

Setting:
Single institution tertiary academic center, 2011 to 2020.

Patients:
Seventy-seven consecutive patients.

Interventions:
Scalene muscle BTI for nTOS with or without surgical decompression.

Main Outcome Measures:
Pain relief and Quick Disability of the Arm, Shoulder and Hand (QDASH) score.

Results:
Seventy-seven patients, with a mean age of 31.4 years, had BTI for symptoms of nTOS. All patients underwent pretreatment physical therapy through the Edgelow protocol for a mean duration of 3.4 months. However, 72.7% had dynamic vascular compression on duplex ultrasound with provocative maneuvers and 85.7% had a positive physical examination finding. After BTI, 77.9% reported subjective relief, confirmed by an improved QDASH disability score. Thirty-one patients (40.3%) then went on to have further persistent symptoms and proceeded with first rib resection. After BTI + Surgery, 96.8% reported symptomatic relief and had a median QDASH score improvement of 21 (range: 10-40), with all reaching minimal clinically important differences in the QDASH score after combination therapy.

Conclusions:
In this reported series of chemodenervation in patients with nTOS, BTI is helpful in alleviating symptoms before definitive surgical decompression. BTI followed by first rib resection provides additional symptom improvement over BTI alone.
Primary central nervous system lymphoma: advances in its pathogenesis, molecular markers and targeted therapies
Authors: Hernández-Verdin Isaias , Morales-Martínez Andrea , Hoang-Xuan Khê , Alentorn Agustí 
Published: November 2022

Purpose of review
Primary central nervous system lymphoma (PCNSL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL) located in the CNS with a less favorable prognosis. Recent information addressing the disease molecular heterogeneity is paving the way for tailored treatment strategies. This article reviews current work on the pathogenesis of the disease, potential biomarkers, and treatments.

Recent findings
Previous molecular classifications of PCNSL, built on DLBCL heterogeneity, did not properly address its intrinsic variability. Recent evidence has shown the existence of four different molecular PCNSL subtypes with associated multiomic characteristics, including prognostic relevance. Several studies have identified the tumor microenvironment (TME) as a driving prognostic factor in PCNSL. Therapy efforts continue mainly into targeting either the NF-κβ (nuclear factor kappa-light-chain enhancer of activated B cells) pathway or modulating the TME through immunomodulatory drugs (lenalidomide) or immunotherapy (antiprogrammed cell death 1/programmed cell death 1 ligand 1).

Summary
Despite the increasing understanding of PCNSL pathogenesis with recent studies, future efforts are still needed to yield diagnostic biomarkers to detect either PCNSL or its molecular subtypes and hence ease routine clinical use.
Effects of surrounding frames and inner targeted line segments on event-related potentials in geometric-optical illusions
Authors: Yang Lan , Sui Li 
Published: November 2022

Objective
The Sander illusion and the horizontal-vertical (H-V) illusion are both size and orientation geometric-optical illusions. The Sander geometric figures can be simply regarded as being made up of surrounding frames and inner targeted line segments. Similarly, H-V illusory geometric figures are made up of the targeted line segments. The role of surrounding frames and inner targeted line segments in the perception and cognition of geometric-optical illusions is not well understood.

Methods
The time course of event-related potentials (ERP) and the ERP-based standardized low-resolution electromagnetic tomography (sLORETA) source localization were investigated in the Sander illusion and the H-V illusion, which had the same length as the targeted line segments, respectively. The P1, N1, P2, N2 and P3 components of the ERP were focused and measured.

Results
The ERP results demonstrated that the existence of surrounding frames in the Sander illusions-induced significant alterations in the P1, N1, P2, N2 and P3 components, compared with the H-V illusion without surrounding frames. In the Sander illusion, different tilted line segments and surrounding frames resulted in significant differences in the P2, N2 and P3 components. The sLORETA results also demonstrated brain activities of source localization as a function of the surrounding frames and the tilted inner line segments.

Conclusions
These findings implicate that the perceptual and cognitive processes of the geometric-optical illusions are correlated to the surrounding frames/background, as well as the orientation/direction of inner targeted line segments in geometric figures.
Mobility and ART retention among men in Malawi: a mixed methods study
Authors: Thorp Marguerite , Bellos MacDaphton , Temelkovska Tijana , Mphande Misheck , Cornell Morna , Hubbard Julie , Choko Augustine , Coates Tom , Hoffman Risa , Dovel Kathryn 
Published: November 2022

AbstractIntroductionMobility is associated with worse outcomes across the HIV treatment cascade, especially among men. However, little is known about the mechanisms that link mobility and poor HIV outcomes and what types of mobility most increase the risk of treatment interruption among men in southern Africa.MethodsFrom August 2021 – January 2022, we conducted a mixed-methods study with men living with HIV (MLHIV) but not currently receiving antiretroviral therapy (ART) in Malawi. Data collection was embedded within two larger trials (ENGAGE and IDEaL trials). We analyzed baseline survey data of 223 men enrolled in the trials who reported being mobile (defined as spending ≥14 nights away from home in the past 12 months) using descriptive statistics and logistic regression. We then recruited 32 men for in-depth interviews regarding their travel experiences and ART utilization. We analyzed qualitative data using constant comparative methods.ResultsSurvey data showed that 34% of men with treatment interruptions were mobile, with a median of 60 nights away from home in the past 12 months; 69% of trips were for income generation. More nights away from home in the past 12 months and having fewer household assets were associated with longer periods out of care. In interviews, men reported that travel was often unplanned, and men were highly vulnerable to exploitive employer demands, which led to missed appointments and ART interruption. Men made major efforts to stay in care but were often unable to access care on short notice, were denied ART refills at non-home facilities, and/or were treated poorly by providers, creating substantial barriers to remaining in and returning to care. Men desired additional multi-month dispensing (MMD), the ability to refill treatment at any facility in Malawi, and streamlined pre-travel refills at home facilities.ConclusionsMen prioritize ART and struggle with the trade-offs between their own health and providing for their families. Mobility is an essential livelihood strategy for MLHIV in Malawi, but it creates conflict with ART retention, largely due to inflexible health systems. Targeted counseling and peer support, access to ART services anywhere in country, and MMD may improve outcomes for mobile men.
Identification of small molecules with virus growth enhancement properties
Authors: Jesús García-Murria Ma , Gadea-Salom Laura , Moreno Sandra , Zaragoza Oscar , Brun Alejandro , Mingarro Ismael , Martínez-Gil Luis 
Published: November 2022

AbstractThe novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused the pandemic disease known as coronavirus disease 2019 (COVID-19). COVID-19 vaccines were developed at record speed and were authorized approximately a year after the original outbreak. This fast response saved the lives of countless individuals and reduced the disease burden of many more. The experience has served as a reminder of the necessity to implement solid vaccine development platforms and fast production pipelines. Manufacturing vaccines for enveloped viruses, including some SARS-CoV-2 vaccines, often relies on the production of large quantities of viruses in vitro. Thus, speeding up or increasing virus production would expedite vaccine development. With this objective in mind, we established a high throughput screening (HTS) to identify small molecules that enhance or speed up host-virus membrane fusion. Among the HTS hits, we identified that ethynylestradiol augments SARS-CoV-2 fusion activity in both the absence and presence of TMPRSS2. Furthermore, we confirmed that ethynylestradiol can boost the growth of not only SARS-CoV-2 but also Influenza A virus in vitro. A small molecule with these characteristics could be implemented to improve vaccines production.ImportanceThe (COVID-19) pandemic had a tremendous impact on our healthcare systems and the global economy. The rapid development of effective vaccines saved the lives of countless individuals and reduced the disease burden of many more. Intending to increase vaccine production, we developed and performed a high-throughput screening (HTS) to identify small molecules that enhance viral and cellular membrane fusion. Among the HTS hits, we confirmed that Ethynylestradiol can boost the growth of SARS-CoV-2 and Influenza A virusin vitro.