bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Initiation of Antiretroviral Therapy is Protective Against Seizures in Children With HIV in Zambia: A Prospective Case–Control Study
Authors: Bearden David R. , Mwanza-Kabaghe Sylvia , Bositis Christopher M. , Dallah Ifunanya , Johnson Brent A. , Siddiqi Omar K. , Elafros Melissa A. , Gelbard Harris A. , Okulicz Jason F. , Kalungwana Lisa , Musonda Nkhoma , Theodore William H. , Mwenechanya Musaku , Mathews Manoj , Sikazwe Izukanji T. , Birbeck Gretchen L. 
Published: November 2023

Background:
Seizures are relatively common among children with HIV in low- and middle-income countries and are associated with significant morbidity and mortality. Early treatment with antiretroviral therapy (ART) may reduce this risk by decreasing rates of central nervous system infections and HIV encephalopathy.

Methods:
We conducted a prospective, unmatched case–control study. We enrolled children with new-onset seizure from University Teaching Hospital in Lusaka, Zambia and 2 regional hospitals in rural Zambia. Controls were children with HIV and no history of seizures. Recruitment took place from 2016 to 2019. Early treatment was defined as initiation of ART before 12 months of age, at a CD4 percentage >15% in children aged 12–60 months or a CD4 count >350 cells/mm3 for children aged 60 months or older. Logistic regression models were used to evaluate the association between potential risk factors and seizures.

Results:
We identified 73 children with new-onset seizure and compared them with 254 control children with HIV but no seizures. Early treatment with ART was associated with a significant reduction in the odds of seizures [odds ratio (OR) 0.04, 95% confidence interval: 0.02 to 0.09; P < 0.001]. Having an undetectable viral load at the time of enrollment was strongly protective against seizures (OR 0.03, P < 0.001), whereas history of World Health Organization Stage 4 disease (OR 2.2, P = 0.05) or CD4 count <200 cells/mm3 (OR 3.6, P < 0.001) increased risk of seizures.

Conclusions:
Early initiation of ART and successful viral suppression would likely reduce much of the excess seizure burden in children with HIV.
Triangulation of a Needs Assessment on High-Tone Pelvic Floor Dysfunction
Authors: Smith Devon , Gugerty Lindsey , Schug Seran , Lipetskaia Lioudmila 
Published: November 2023

Importance
High-tone pelvic floor dysfunction is a complex condition that is challenging to manage effectively. Pelvic floor physical therapy (PFPT) is often used in the treatment and relies on a coordinated effort between the physician, patient, and physical therapist. Collaboration is crucial for therapy success, but there is limited research that includes personal perspectives from these individuals.

Objective
The objective of this qualitative study was to gain further insight from these groups to identify areas for improvement in patient counseling and understanding of the diagnosis of high-tone pelvic floor dysfunction and the role of physical therapy.

Study Design
The following participants were recruited: urogynecologists, pelvic floor physical therapists, and patients. Semistructured interviews were conducted exploring participant experiences with therapy and management of the condition and surrounding phenomena.

Results
Participants interviewed included 5 urogynecologists, 5 pelvic floor physical therapists, and 15 patients. Similarities in key themes were identified: (1) the usefulness of pelvic models and illustrations in counseling, (2) appropriate descriptions of therapy, (3) motivating factors for patients, and (4) patient barriers to completing therapy. Several emergent themes revealed a misalignment in perspectives, including (1) patients reporting an unclear understanding of PFPT, (2) patient unawareness of the intimacy of therapy, and (3) reports of unsupportive and unempathetic physician providers.

Conclusions
There are both similarities and discrepancies in the perspectives among physicians, pelvic floor physical therapists, and patients regarding high-tone pelvic floor dysfunction and PFPT. Acknowledging these comparisons and adapting practices could facilitate patient-centered care and improve patient understanding of their diagnosis.
Empowering nurses to increase engagement in advance care planning in a medicine transitional care unit: a best practice implementation project
Authors: Garcia Philip , Kim Hannah Jang , Barbour Susan , Cooper Adam S. 
Published: November 2023

ABSTRACT

Introduction and objective:
Advance care planning (ACP) communication and documentation are often inadequate, leading to care that is inconsistent with patients’ preferences and moral dilemmas for family members. Nurses are patient advocates optimally positioned to initiate ACP but many feel that they lack the training and skills to navigate these conversations. The objective of this project was to increase nurses’ capacity to engage in ACP.

Methods:
This project used the JBI audit and feedback method to implement evidence into practice. The JBI Practical Application of Clinical Evidence System and Getting Research into Practice audit tools were used to incorporate ACP into nursing workflow. Eight audit criteria were created based on a JBI evidence summary. Compliance was measured by reviewing ACP notes from electronic health records and online survey responses. A baseline audit was followed by educational presentations and development of posted materials. Three follow-up audits examined sustainability.

Results:
Compliance with the best practice recommendation for nurses to engage in ACP discussions increased from 55% to 80%. There was improvement from zero ACP notes at baseline (0% compliance) to 12 ACP notes in the final audit. Of these notes, 42% included all best practice elements and 92% included patients’ treatment preferences.

Conclusions:
Development of an integrative nursing education plan for ACP empowers nurses to engage in vital conversations. Informing nurses of their scope of practice, defining terms and expectations, and encouraging them to attempt and document conversations will benefit patients. Future initiatives would benefit from incorporating practical opportunities without real-life implications and providing continued support to cohorts.
COVID-19 infection wave mortality from surveillance data in the Philippines using machine learning
Authors: Migriño Julius R , Batangan Ani Regina U , Abello Rizal Michael R 
Published: November 2023

ABSTRACTObjectiveThe Philippines has had several COVID-19 infection waves brought about by different strains and variants of SARS-CoV-2. This study aimed to describe COVID-19 outcomes by infection waves using machine learning.MethodsWe used a cross-sectional surveillance data review design using the DOH COVID DataDrop data set as of September 24, 2022. We divided the data set into infection wave data sets based on the predominant COVID-19 variant(s) of concern during the identified time intervals: ancestral strain (A0), Alpha/Beta variant (AB), Delta variant (D), and Omicron variant (O). Descriptive statistics and machine learning models were generated from each infection wave data set.ResultsOur final data set consisted of 3 896 206 cases and ten attributes including one label attribute. Overall, 98.39% of cases recovered while 1.61% died. The Delta wave reported the most deaths (43.52%), while the Omicron wave reported the least (10.36%). The highest CFR was observed during the ancestral wave (2.49%), while the lowest was seen during the Omicron wave (0.61%). Higher age groups generally had higher CFRs across all infection waves. The A0, AB and D models had up to four levels with two or three splits for each node. The O model had eight levels, with up to 16 splits in some nodes. Of the ten attributes, only age was included in all the decision tree models, while region of residence was included in the O model. F-score and specificity were highest using naïve Bayes in all four data sets. Area under the curve (AUC) was highest in the naïve Bayes models for the A0, AB and D models, while sensitivity was highest in the decision tree models for the A0, AB and O models.DiscussionThe ancestral, Alpha/Beta and Delta variants seem to have similar transmission and mortality profiles. The Omicron variant caused lesser deaths despite being more transmissible. Age remained a significant predictor of death regardless of infection wave. We recommend constant timely analysis of available data especially during public health events and emergencies.
Expansion of human hematopoietic stem cells by inhibiting translation
Authors: Li Chenchen , Shin Hanna , Bhavanasi Dheeraj , Liu Mai , Yu Xiang , Peslak Scott A. , Liu Xiaolei , Alvarez-Dominguez Juan R. , Blobel Gerd A. , Gregory Brian D. , Huang Jian , Klein Peter S. 
Published: November 2023

AbstractHematopoietic stem cell (HSC) transplantation using umbilical cord blood (UCB) is a potentially life-saving treatment for leukemia and bone marrow failure but is limited by the low number of HSCs in UCB. The loss of HSCs after ex vivo manipulation is also a major obstacle to gene editing for inherited blood disorders. HSCs require a low rate of translation to maintain their capacity for self-renewal, but hematopoietic cytokines used to expand HSCs stimulate protein synthesis and impair long-term self-renewal. We previously described cytokine-free conditions that maintain but do not expand human and mouse HSCs ex vivo. Here we performed a high throughput screen and identified translation inhibitors that allow ex vivo expansion of human HSCs while minimizing cytokine exposure. Transplantation assays show a ∼5-fold expansion of long-term HSCs from UCB after one week of culture in low cytokine conditions. Single cell transcriptomic analysis demonstrates maintenance of HSCs expressing mediators of the unfolded protein stress response, further supporting the importance of regulated proteostasis in HSC maintenance and expansion. This expansion method maintains and expands human HSCs after CRISPR/Cas9 editing of theBCL11A+58enhancer, overcoming a major obstacle to ex vivo gene correction for human hemoglobinopathies.
Acute loss of fingertip sensation leads to general compensatory changes in eye-hand coordination
Authors: Ung Kevin , Yau Jeffrey M. , Nordmark Per F 
Published: November 2023

AbstractThe role of sensory feedback is well established in current models of motor control, evidenced by deficits in movement coordination resulting from impaired sensory function. When vision and touch are both available for object-oriented manual behaviors, these senses can be distinctly leveraged; vision guides movement planning while touch provides feedback on hand-object interactions. How eye-hand coordination changes with the loss of somatosensory feedback has not been well studied. Conceivably, vision is recruited to compensate for the feedback lost when touch is abolished. We tested healthy participants on a manual dexterity task, consisting of moving small metal pegs. The task was performed before and after administration of digital anesthesia that abolished cutaneous sensations while preserving motor function with the acting hand. During peg collection, transport, and placement epochs, we tracked gaze direction and hand positions while also recording forces applied to the pegboard. We hypothesized that the nervous system selectively adapts eye-hand coordination according to the dexterity demands of the task epochs. We found that participants maintained the ability to perform the pegboard task following the loss of cutaneous feedback, albeit with longer trial times and altered force profiles. Notably, somatosensory loss was accompanied by a shift in visual behavior marked by a closer alignment between gaze and hand positions during all task epochs, even those that did not involve object manipulation. Together, these data affirm the contributions of sensory feedback to force control in service of dexterous object manipulation and reveal the non-selective nature of compensatory eye-hand coordination processes.Significance StatementTouch and vision typically support distinct, but coordinated aspects of dexterous manual behaviors. Here, we evaluated how acute removal of tactile feedback using digital anesthesia affected performance and eye-hand coordination in a manual dexterity task. With insensate fingers and intact vision, participants continued to perform the task successfully, albeit with longer trial times and altered force profiles. We also observed closer alignment between gaze and hand positions during all task epochs, even those that did not involve object manipulation. Our results reveal the consequences of acute somatosensory loss and the general nature of compensatory eye-hand coordination processes.
Intermittent cell division dynamics in regenerating Arabidopsis roots reveals complex long-range interactions
Authors: Fallesen T. , Amarteifio S. , Pruessner G. , Jensen H. J. , Sena G. 
Published: November 2023

ABSTRACTIn this work, we present a quantitative comparison of the cell division dynamics between populations of intact and regenerating root tips in the plant model systemArabidopsis thaliana. To achieve the required temporal resolution and to sustain it for the duration of the regeneration process, we adopted a live imaging system based on light-sheet fluorescence microscopy, previously developed in the laboratory. We offer a straightforward quantitative analysis of the temporal and spatial patterns of cell division events showing a statistically significant difference in the frequency of mitotic events and spatial separation of mitotic event clusters between intact and regenerating roots.
VHL loss enables immune checkpoint blockade therapy by boosting type I interferon response
Authors: Jiao Meng , Bao Xuhui , Hu Mengjie , Pan Dong , Liu Xinjian , Kim Jonathan , Li Fang , Li Chuan-Yuan 
Published: November 2023

AbstractDespite a moderate mutation burden, clear cell renal cell carcinoma (ccRCC) responds well to immune checkpoint blockade (ICB) therapy. Here we report that loss-of-function mutations in the von Hippel-Lindau (VHL) gene, the most frequent in ccRCC, underlies its responsiveness to ICB therapy. We demonstrate that genetic knockout of theVHLgene enhanced the efficacy of anti-PD-1 therapy in multiple murine tumor models in a T cell-dependent manner. Mechanistically, we discovered that upregulation of HIF1α and HIF2α induced by VHL gene loss decreased mitochondrial outer membrane potential and caused the cytoplasmic leakage of mitochondrial DNA (mtDNA), which triggered cGAS-STING activation and induced type I interferons. Our study thus provided novel mechanistic insights into the role of VHL gene loss in potentiating ccRCC immunotherapy.
Role of a holo-insertase complex in the biogenesis of biophysically diverse ER membrane proteins
Authors: Page Katharine R. , Nguyen Vy N. , Pleiner Tino , Tomaleri Giovani Pinton , Wang Maxine L. , Guna Alina , Wang Ting-Yu , Chou Tsui-Fen , Voorhees Rebecca M. 
Published: November 2023

SUMMARYMammalian membrane proteins perform essential physiologic functions that rely on their accurate insertion and folding at the endoplasmic reticulum (ER). Using forward and arrayed genetic screens, we systematically studied the biogenesis of a panel of membrane proteins, including several G-protein coupled receptors (GPCRs). We observed a central role for the insertase, the ER membrane protein complex (EMC), and developed a dual-guide approach to identify genetic modifiers of the EMC. We found that the back of sec61 (BOS) complex, a component of the ‘multipass translocon’, was a physical and genetic interactor of the EMC. Functional and structural analysis of the EMC•BOS holocomplex showed that characteristics of a GPCR’s soluble domain determine its biogenesis pathway. In contrast to prevailing models, no single insertase handles all substrates. We instead propose a unifying model for coordination between the EMC, multipass translocon, and Sec61 for biogenesis of diverse membrane proteins in human cells.
Exploring the molecular composition of the multipass translocon in its native membrane environment
Authors: Gemmer Max , Chaillet Marten L. , Förster Friedrich 
Published: November 2023

AbstractMultispanning membrane proteins are inserted into the endoplasmic reticulum membrane by the ribosome-bound multipass translocon machinery. Based on cryo-electron tomography and extensive subtomogram analysis, we reveal the composition and arrangement of multipass translocon components in their native membrane environment. The intramembrane chaperone complex PAT and the translocon associated protein (TRAP) complex associate substoichiometrically with the multipass translocon in a translation-dependent manner. While PAT is preferentially recruited to active complexes, TRAP primarily associates with inactive translocons. The subtomogram average of the TRAP-multipass translocon reveals intermolecular contacts between the luminal domains of TRAP and an unknown subunit of the BOS complex. AlphaFold modeling suggests this protein is NOMO, bridging the luminal domains of nicalin and TRAPα. Collectively, our results visualize the interplay of accessory factors associated with multipass membrane protein biogenesis under near-native conditions.
Coexpression enhances cross-species integration of scRNA-seq across diverse plant species
Authors: Passalacqua Michael John , Gillis Jesse 
Published: November 2023

AbstractSingle-cell RNA sequencing is increasingly used to investigate cross-species differences driven by gene expression and cell-type composition in plants. However, the frequent expansion of plant gene families due to whole genome duplications makes identification of one-to-one orthologs difficult, complicating integration. Here, we demonstrate that coexpression can be used to identify non-orthologous gene pairs with proxy expression profiles, improving the performance of traditional integration methods and reducing barriers to integration across a diverse array of plant species.
Incidence, prevalence, and survival of breast cancer in the United Kingdom from 2000-2021: a population-based cohort study
Authors: Barclay Nicola L , Burn Edward , Delmestri Antonella , Duarte-Salles Talita , Golozar Asieh , Man Wai Yi , Tan Eng Hooi , Tietzova Ilona ,   OPTIMA Consortium, Prieto-Alhambra Daniel , Newby Danielle 
Published: November 2023

ABSTRACTBackgroundBreast cancer is the most frequently diagnosed cancer in females globally. However, we know relatively little about trends in males. This study describes UK secular trends in breast cancer from 2000-2021 for both sexes.MethodsPopulation-based cohort study using UK primary care Clinical Practice Research Datalink (CPRD) GOLD database and validated in Aurum. There were 5848436 eligible females and 5539681 males aged 18+ years, with ≥one year of prior data availability in the study period. We estimated breast cancer incidence rates (IR), period prevalence (PP) and survival at one-, five- and 10-years after diagnosis using the Kaplan-Meier method. Analyses were further stratified by age.ResultsIR of breast cancer from 2000-2021 was 194.4 per 100000 person-years for females and 1.16 for males. PP in 2021 was 2.1% for females and 0.009% for males. Both sexes have seen around a 2.5-fold increase in PP across time. Incidence increased with age for both sexes, peaking in females aged 60-69 years and males 90+. There was a drop in incidence for females aged 70-79 years. From 2003-2019, incidence increased >2-fold in younger females (aged 18-29: IR 2.12 in 2003 vs. 4.58 in 2018); decreased in females aged 50-69 years; and further declined from 2015 onwards in females aged 70-89 years. Survival for females after one-, five-, and ten-years after diagnosis was 95.1%, 80.2%, and 68.4%, and for males 92.9%, 69.0%, and 51.3%. Survival at one-year increased by 2.08% points, and survival at five years increased by 5.39% from 2000-2004 to 2015-2019 for females, particularly those aged 50-70 years. For males, there were no clear time-trends for short-term and long-term survival.ConclusionChanges in incidence of breast cancer in females largely reflect the success of screening programmes, as rates rise and fall in synchronicity with ages of eligibility for such programmes. Overall survival from breast cancer for females has improved from 2000 to 2021, again reflecting the success of screening programmes, early diagnosis, and improvements in treatments. Male breast cancer patients have worse survival outcomes compared to females, highlighting the need to develop male-specific diagnosis and treatment strategies to improve long-term survival in line with females.
Hearing Progression of Children with Enlarged Vestibular Aqueduct (EVA) According toSLC26A4Genetic Mutation Status
Authors: Osborne Madeline Hocking , Koeritzer Margaret , Herd Hannah , Polonenko Melissa Jane 
Published: November 2023

AbstractEnlarged vestibular aqueduct (EVA) is a malformation associated with sensorineural hearing loss in children. Mutations in theSLC26A4gene are also associated with EVA and may contribute to more severe hearing losses that progress, but the timescale of this progression remains unknown. Given that children undergo significant speech and language development, a better understanding of the timing and extent of hearing loss is needed for individuals who have EVA. Through a retrospective review of records in a local database, we aimed to 1) estimate the prevalence of aSLC26A4mutation in this pediatric EVA cohort; and 2) compare hearing threshold severity and timing of progression across children who have EVA and differentSLC26A4statuses. Of 62 children with EVA, 39 had available genetic results and of these, 15 had at least one mutation of theSLC26A4gene (38%). The children with aSLC26A4mutation had a more severe onset of hearing loss and a more rapid progression of hearing loss over time, especially for higher frequencies, than children without a mutation in this gene. This longitudinal information may facilitate prognostic counseling to pediatric patients and better inform the audiology follow-up appointments for these families.