bluuebunny/crossref_metadata_2025_split huggingface dataset:
Good and bad indications for adjuvant radiotherapy after transoral laser microsurgery for laryngeal cancer
Authors: Sampieri Claudio , Ruiz-Sevilla Laura , Vilaseca Isabel 
Published: January 2025

Purpose of review
To summarize current evidence regarding the indication of adjuvant treatment after transoral laser microsurgery (TOLMS).

Recent findings
Apart from well known risk factors, margins represent the key point in the decision-making. If margins are affected, additional treatment is mandatory. One exception could be the presence of one superficial margin in early tumors that can be strictly followed up by fiberendoscopy. As a general rule, the best option is margin-revision surgery by repeating TOLMS or switching to open partial surgery. (Chemo)radiotherapy can be also considered, being total laryngectomy the last alternative. In locally advanced tumors with uncertain margins (e.g. posterior paraglottic space invasion, vertical anterior commissure reaching the cartilage during primary resection), adjuvant treatment may improve local control with laser but with little impact on disease-specific or overall survival. In this scenario, QoL may be in part reduced after radiotherapy, although recent studies suggest that functional outcomes are favorable. Therefore, decision should be discussed individually with the patient, especially if a total laryngectomy is the only alternative after a possible relapse.

Summary
Considerable work needs to be done to identify those cases that may benefit from adjuvant treatment after TOLMS, including a detailed description of functional outcomes.
Exploring Rehabilitation Protocols for Primary Anterior Cruciate Ligament Repair: Insights from a Scoping Review
Authors: Chang Alan , Chan Cheng-Yen , Lin Meng-Tin , Wu Chueh-Hung , Özçakar Levent 
Published: January 2025

Abstract

Objectives
The primary repair of the anterior cruciate ligament (ACL) has re-emerged as a treatment for acute ruptures. While numerous studies have investigated rehabilitation after ACL reconstruction, few have focused on primary repair. We aimed to describe the rehabilitation protocols for primary ACL repair, and to identify knowledge gaps and differences between primary ACL repair and reconstruction.

Design
A scoping review design was selected due to the descriptive and exploratory nature, aiming to identify and map available research evidence from various databases relevant to the research question. Evaluation of study quality and risk of bias is not required in scoping reviews.

Results
A comprehensive search of PubMed, Embase, Cochrane Library, and Web of Science identified a total of 66 studies involving over 3,100 participants. No randomized controlled trials directly comparing postoperative rehabilitation protocol were identified. Eight items of the rehabilitation protocols were analyzed, based on existing clinical practice guidelines for ACL reconstruction. This review highlights the inadequacy and heterogeneity of the available data.

Conclusions
This review revealed a lack of consistent evidence and call for the development of standardized, technique-specific rehabilitation guidelines after primary ACL repair. Clinical trials and transparent reporting are needed to establish validated protocols.
Impact of body-height increase on gastrocnemius muscle stiffness in children with cerebral palsy: A one-year prospective cohort study
Authors: Nakamura Shinya , Kimoto Minoru , Wakasa Masahiko , Saito Akira , Sakamoto Hitoshi , Misawa Akiko , Kawanobe Uki , Okada Kyoji 
Published: January 2025

Abstract

Objective
To investigate whether the impacts of height increase on gastrocnemius muscle (GM) stiffness are greater in children with spastic cerebral palsy (CP) than in those with typical development (TD).

Design
This one-year cohort study enrolled children (CP, 23; TD, 23) who underwent two measurements conducted at entry and after one year. Lateral and medial GM-strain ratios representing muscle stiffness were obtained using elastography.

Results
All regression equations (dependent variable, rate of change [RoC] of height; independent variable, RoC of the GM-strain ratios) were significant and all R
2s in children with CP (all p < 0.001; lateral GM’s R
2 = 0.81; medial GM’s R
2 = 0.74) were greater than those in children with TD (p < 0.001 and R
2 = 0.49; medial GM’s R
2 = 0.49). The coefficients of equations in children with CP were significantly larger than those in TD (p < 0.05).

Conclusion
The greater R
2 values in CP than TD could explain how the variation in height predicts the variations in GM stiffness more accurately in CP than in TD. GM stiffness worsens more in children with CP than that in TD.
Late re-engagement into HIV care among adults in the Swiss HIV Cohort Study
Authors: Haas Andreas D , Kusejko Katharina , Cavassini Matthias , Günthard Huldrych , Stöckle Marcel , Calmy Alexandra , Bernasconi Enos , Schmid Patrick , Egger Matthias , Wandeler Gilles ,   the Swiss HIV Cohort Study
Published: January 2025

Introduction:
Little is known about the clinical status of persons with HIV (PWH) who re-engage in care after an interruption. We evaluated the immunological and clinical characteristics of individuals re-engaging in care within the Swiss HIV Cohort Study.

Methods:
Participants who re-engaged in care after an interruption >14 months with a viral load ≥100 copies/mL were classified as having interrupted ART. We defined late re-engagement as re-engaging with a CD4 cell count of <350 cells/µL or a new CDC stage C disease. Linear and logistic regression models with restricted cubic splines were used to estimate the mean CD4 cell count at re-engagement and the probability of late re-engagement as a function of care interruption duration.

Results:
Of 14,864 participants with a median follow-up of 10.2 years (IQR 4.7-17.2 years), 2,768 (18.6%) interrupted care, of whom 1,489 (53.8%) re-engaged. Among those re-engaging, 62.3% had interrupted ART. For participants who interrupted ART, the mean CD4 count declined from 374 cells/µL (95% CI 358-391 cells/µL) before the interruption to 250 cells/µL (95% CI 221-281 cells/µL) among those re-engaging after 14 months, and to 185 cells/µL (95% CI 160-212 cells/µL) among those re-engaging after 60 months. The estimated risk of late re-engagement in care was 68.6% (95% CI 62.3-74.4%) for participants who interrupted ART for 14 months and 75.2% (95% CI 68.9-80.6%) for those who interrupted ART for 60 months.

Conclusion:
Although HIV care interruptions are not very common in Switzerland, the majority of PWH re-engaging after interrupting ART return with late-stage HIV.
Resolution of Neuropsychiatric Adverse Events After Switching to a Doravirine-Based Regimen in the Open-Label Extensions of the DRIVE-AHEAD and DRIVE-FORWARD Trials
Authors: Moyle Graeme , Meng Fanxia , Wan Hong , Sklar Peter , Plank Rebeca M. , Lahoulou Rima 
Published: January 2025

Background:
Neuropsychiatric adverse events (NPAEs) are associated with several antiretrovirals. Doravirine (DOR), a non-nucleoside reverse transcriptase inhibitor indicated for HIV-1 treatment, does not interact significantly with known neurotransmitter receptors in vitro. First-line therapy with DOR-based regimens resulted in significantly fewer NPAEs than efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) and similar rates to those of ritonavir-boosted darunavir (DRV/r) with 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) through Week 96 of the phase 3 DRIVE-AHEAD and DRIVE-FORWARD studies, respectively.

Methods:
In DRIVE-AHEAD (NCT02403674) and DRIVE-FORWARD (NCT02275780), treatment-naive adults randomly received DOR/lamivudine/TDF or EFV/FTC/TDF and DOR + 2 NRTIs or DRV/r + 2 NRTIs, respectively, for a 96-week double-blind phase; afterward, participants could continue or switch to a DOR-based regimen for a 96-week open-label extension.

Results:
Overall, 269 and 233 participants in DRIVE-AHEAD and DRIVE-FORWARD, respectively, switched to a DOR-based regimen. At Week 96, 26 and 15 participants randomized to EFV/FTC/TDF and DRV/r + 2 NRTIs, respectively, had ongoing NPAEs, resolving by Week 192 in 73% (19/26) and 40% (6/15) of participants switching to a DOR-based regimen. New-onset NPAEs were reported by 9% (25/269) and 8% (18/233) of participants; by Week 192, new-onset NPAEs were resolved and/or resolving in 60% (15/25) and 61% (11/18) of participants.

Conclusions:
In both trial extensions, NPAEs persisted in 3–4% of participants 96 weeks after switching to a DOR-based regimen, possibly representing the background rate for these events. This suggests DOR-based therapy may be a good option for adults with baseline neuropsychiatric symptoms or those experiencing NPAEs with other antiretrovirals.
Quality of Sexual Life Before and After Pelvic Organ Prolapse Surgery
Authors: Wihersaari Olga A.E. , Karjalainen Päivi , Tolppanen Anna-Maija , Mattsson Nina , Nieminen Kari , Jalkanen Jyrki 
Published: January 2025

Importance
Although surgery for pelvic organ prolapse (POP) is generally associated with an improvement in sexual function, knowledge on specific changes is limited.

Objectives
The aim of this study was to describe and compare changes in sexual activity and function during a 5-year follow-up period after POP surgery.

Study Design
This was a nationwide cohort study of 3,515 women operated on for POP in 2015 in Finland. Sexual activity and function were assessed preoperatively and 6 months, 2 years, and 5 years after native tissue and mesh-augmented surgery using the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire Short Form (PISQ-12).

Results
The PISQ-12 score improved significantly at 6-month follow-up, regardless of surgical approach. Negative emotional reactions (relative risk [RR], 0.21; 95% confidence interval [CI], 0.13–0.36), orgasm intensity (RR, 4.23; 95% CI, 2.94–6.07), and avoidance of sexual intercourse due to fear of incontinence (RR, 0.25; 95% CI, 0.15–0.43) or bulging (RR, 0.11; 95% CI, 0.07–0.17) improved remarkably at 6 months and remained up to 5 years after surgery. Satisfaction (RR, 1.10; 95% CI, 1.04–1.18), coital pain (RR, 0.71; 95% CI, 0.51–0.99), and coital incontinence (RR, 0.48; 95% CI, 0.15–0.43) improved only at 6-month follow-up. Among women with deteriorated sexual function, the decline was associated with loss of excitement and satisfaction, increased coital pain, and partner’s erectile problems. Partner-related factors and lack of sexual desire were main reasons for sexual inactivity both preoperatively and postoperatively.

Conclusions
Considering patient’s sexual wellbeing and informing them of the expected changes in individual sexual function items are important aspects of preoperative counseling. This may reduce false hopes regarding the effect of surgery on sexual function and improve postoperative patient satisfaction.
Self-other mentalizing and attachment insecurity in the dimensional model of personality disorders: From research to clinical practice
Authors: Jańczak Monika Olga , Górska Dominika , Jurek Paweł , Taubner Svenja 
Published: January 2025

AbstractBackgroundResearch on different aspects of mentalizing is essential for understanding the mechanisms underlying personality disorders (PD) and informing psychotherapy approaches, where mentalizing functions as a key mechanism of change. This study aimed to explore whether self- and other-mentalizing, in interaction with attachment insecurity, differentially explain Criteria A (level of personality functioning) and B (maladaptive traits) of the Alternative Model for Personality Disorders in the DSM-5.MethodOur sample consisted of 109 participants (54% female, 41% male, 5% nonbinary). We used The Structured Clinical Interview for DSM-5 Personality Disorders, A Movie for the Assessment of Social Cognition, the Reflective Functioning Questionnaire, the Experiences in Close Relationships – Revised, The Self and Interpersonal Functioning Scale, and The Personality Inventory for DSM-5.ResultsRegression analyses show that self-mentalizing deficits uniquely predict both Criterion A domains (self and interpersonal functioning) and all five maladaptive traits, while other-mentalizing is relevant only to interpersonal functioning. Explained variance (adjusted R²) ranges from 55% to 18%. Additionally, mentalization moderates the relationship between insecure attachment and personality pathology (Interpersonal functioning, Negative Affectivity and Detachment), mainly with greater mentalization deficits linked to more severe personality dysfunction under heightened attachment insecurity.ConclusionOur findings authorize mentalizing as a crucial factor in PD, supporting the potential value of mentalization-focused interventions in addressing both the severity and the “flavor” of PD. Notably, our findings suggest a hierarchy within self- and other-mentalizing, indicating that self-mentalizing plays a more foundational role in PD. Through a comprehensive, multi-method assessment of mentalization, this study offers a refined understanding of its role in psychopathology, providing valuable insights that could guide the development of more targeted therapeutic interventions.
Pathogenetic mechanisms of muscle-specific ribosomes in dilated cardiomyopathy
Authors: Murphy Michael R. , Ganapathi Mythily , Lee Teresa M. , Fisher Joshua M. , Patel Megha V. , Jayakar Parul , Buchanan Amanda , Rippert Alyssa L , Ahrens-Nicklas Rebecca C. , Nair Divya , Soni Rajesh K. , Yin Yue , Yang Feiyue , Reilly Muredach P. , Chung Wendy K. , Wu Xuebing 
Published: January 2025

AbstractThe heart employs a specialized ribosome in its muscle cells to translate genetic information into proteins, a fundamental adaptation with an elusive physiological role1–3. Its significance is underscored by the discovery of neonatal patients suffering from often fatal heart failure caused by severe dilated cardiomyopathy when both copies of the geneRPL3Lare mutated4–9. RPL3L is a muscle-specific paralog1–3of the ubiquitous ribosomal protein L3 (RPL3), which makes the closest contact of any protein to the ribosome’s RNA-based catalytic center10.RPL3L-linked heart failure represents the only known human disease associated with tissue-specific ribosomes, yet the underlying pathogenetic mechanisms remain poorly understood. Intriguingly, disease is linked to a large number of mostly missense variants inRPL3L, andRPL3L-knockout resulted in no severe heart defect in either human or mice3, 11–13, challenging the prevailing view that autosomal recessive diseases are caused by loss-of-function mutations. Here, we report three new cases ofRPL3L-linked severe neonatal heart failure and present a unifying pathogenetic mechanism by which a large number of variants in the muscle-specific ribosome led to disease. Specifically, affected families often carry one of two recurrent toxic gain-of-function variants alongside a family-specific putative loss-of-function variant. While the non-recurrent variants often trigger partial compensation ofRPL3similar toRpl3l-knockout mice, both recurrent variants exhibit increased affinity for the RPL3/RPL3L chaperone GRWD114–16and 60S biogenesis factors, sequester 28S rRNA in the nucleus, disrupt ribosome biogenesis, and trigger severe cellular toxicity that extends beyond the loss of ribosomes. These findings provide critical insights for genetic screening and therapeutic development of neonatal heart failure. Our results suggest that gain-of-toxicity mechanisms may be more prevalent in autosomal recessive diseases, and a combination of gain-of-toxicity and loss-of-function mechanisms could underlie many diseases involving genes with paralogs.
Rewiring Catalytic Craters: A Path for Engineering β-Glucosidases to Improve Glucose Tolerance
Authors: Suryawanshi Abhishek B. , Bedi Rajiv K. , Pawar Meera , Noronha Santosh , Bhaumik Prasenjit 
Published: January 2025

AbstractBioethanol, a sustainable alternative to fossil fuels, is produced from cellulose via enzymatic saccharification. β-Glucosidase, a key enzyme in this process, hydrolyses disaccharides into glucose but is limited by feedback inhibition. This study investigated GH1 β-glucosidase from a soil metagenome (UnBGl1) to understand and overcome this limitation. We solved the near-atomic resolution crystal structure of UnBGl1 at 1.15 Å as an apo enzyme and report the first high-resolution crystal structures of the enzyme in its pre-hydrolytic state as a cellobiose complex and covalent intermediate-bound state, capturing key stages of its catalytic mechanism. Structural analysis revealed three crucial glucose-binding subsites in UnBGl1’s crater. Glucose binding at the −1 subsite induced a 1.4 Å shift in E370, increasing the distance between catalytic glutamates and reducing enzymatic activity. The C188V variant, generated by rational engineering, significantly improved glucose tolerance to 2.5 M. Additionally, the H261W mutation at the +2 subsite enhanced kinetic properties by improving cellobiose affinity (Km= 22.87 ± 1.1 mM) and shifted the optimal pH to 5.5 from 6.0. Comparative structural analysis with other glucose-tolerant GH1 β-glucosidases revealed conserved residues at the −1 subsite crucial for substrate stabilization and +1 subsite residues interacting with glucose, offering targets for further optimization. Engineered UnBGl1 variants retained high stability and activity on sugarcane bagasse, demonstrating their potential for industrial cellulase cocktails. These findings provide a robust framework for engineering β-glucosidases with enhanced glucose tolerance and catalytic efficiency, paving the way for improved bioethanol production and contributing to sustainable energy solutions.
Development of a Novel Single Cell Multiomics Approach for Simultaneous Analysis of Replication Timing and Gene Expression
Authors: Shetty Anala V. , Steer Clifford J. , Low Walter C. 
Published: January 2025

AbstractReplication timing (RT) allows us to analyze temporal patterns of genome-wide replication, i.e., if genes replicate early or late during the S-phase of the cell cycle. RT has been linked to gene expression in normal and diseased acute and chronic states such as cancer. However, studies done to date focused on bulk cell populations that required tens of thousands of cells for RT analysis. Here, we developed an affordable novel single cell (sc)-multiomics approach to simultaneously analyze RT and gene expression from cells or nuclei. We used this approach to generate sc-RT profiles and sc-gene expression data from the well-established human liver cancer cell line, HepG2. We demonstrated that as few as 17 mid S-phase cells were sufficient to produce cell-type specific pseudo bulk RT profiles that had a high correlation to previously published HepG2 bulk RT profiles. The sc-RT profiles allowed us to visualize how individual cells progressed through genome replication. We were also able to demonstrate high-resolution correlations between RT and gene expression within each individual cell, which to our knowledge, has not been reported. We observed trends that were conserved between individual cells, as well as cell-to-cell variations, which were not possible to detect with the bulk RT studies.
Radial ESWT combined with a specific rehabilitation program (rESWT + RP) is more effective than sham rESWT + RP for acute hamstring muscle complex injury type 3b: a randomized, controlled trial
Authors: Crupnik Javier , Silveti Santiago , Wajnstein Natalia , Rolon Alejandro , Wuerfel Tobias , Stiller Peter , Morral Antoni , Furia John P. , Maffulli Nicola , Schmitz Christoph 
Published: January 2025

ABSTRACTObjectivesThis study tested the hypothesis that radial extracorporeal shock wave therapy combined with a specific rehabilitation program (rESWT + RP) is more effective than sham rESWT + RP in athletes with acute hamstring muscle complex (HMC) injury type 3b.MethodsThis was a prospective, randomized, sham-controlled, single center trial with published protocol, concealed allocation, blinded patients and blinded assessors. A total of 36 semi-professional athletes (soccer, field hockey and rugby players) receiving fees or university scholarships with acute HMC injury type 3b were randomly allocated to rESWT + RP for up to 5 weeks (n=18) or sham rESWT + RP (n=18). The primary outcome was the individual time to return to sport. Secondary outcomes were the individual patient’s satisfaction and presence or absence of re-injury during 6 months post-inclusion into this trial.ResultsNo serious adverse events occurred during the trial. The median / mean time to return to sport was 25.5 / 25.4 ± 3.5 (mean ± SD) days after rESWT + RP (n=18) and 27.5 / 28.3 ± 4.5 days after sham rESWT + RP (n=18) (p=0.037). The mean patient’s satisfaction was not significantly different between the groups. Only one patient in each group experienced a re-injury during 6 months post-inclusion into this trial.ConclusionIn rehabilitation of athletes with acute HMC injury type 3b, rESWT + RP is more effective than sham rESWT + RP.RegistrationClinicalTrials.govIDNCT03473899(registered on March 22, 2018).
EPHA2-dependent Ephrin-B1 signaling supports self-renewal ability and recurrence of oral cancer
Authors: Reshma Raj R , Soumya Krishnan U , Shanmugam Geetha , Datta Nandini , Louis Jiss Maria , Jeyaram Ravichandran Damodaran , Datta Keshava K , Gowda Harsha , Sarkar Meghna , Nair Madhumathy G , Prabhu Jyothy S , Shabeer Hafsa , Balagopal P G , Thameem A , Jose Alan , Maliekal Tessy Thomas 
Published: January 2025

ABSTRACTAs self-renewal of cancer cells is the underlying cause of recurrence and poor prognosis, understanding its molecular determinants is important. Despite the established role of Ephrin-B1 in the regulation of normal stem cells, its role in the self-renewal of cancer cells is poorly explored. Here, using proteomic approach, we report that Ephrin-B1 and its signaling is critical for the self-renewal of oral cancer cells. Further, biochemical analyses revealed that the expression of Ephrin-B1 and EPHA2, a known regulator of cancer stem cells (CSCs), are up-regulated in parallel to the enrichment of self-renewal. Unlike the normal context, as reported, this aberrant upregulation enables theircis-interaction, leading to the phosphorylations of EphrinB1 Y324/329 and Y317. Ourin vitroandin vivofunctional analyses confirmed the role of Ephrin-B1-EPHA2 signaling in enriching CSCs. Using mouse orthotopic models, we show that abrogation of the ligand, receptor or both results in better prognosis. Moreover, the results of thein silicoand immunohistochemical analysis of oral cancer samples reinforced the critical involvement of this signaling in the recurrence of the disease.