bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments
Authors: Loucera Carlos , Carmona Rosario , Esteban-Medina Marina , Bostelmann Gerrit , Muñoyerro-Muñiz Dolores , Villegas Román , Peña-Chilet María , Dopazo Joaquín 
Published: October 2023

AbstractPurposeDespite the extensive vaccination campaigns in many countries, COVID-19 is still a major worldwide health problem because of its associated morbidity and mortality. Therefore, finding efficient treatments as fast as possible is a pressing need. Drug repurposing constitutes a convenient alternative when the need for new drugs in an unexpected medical scenario is urgent, as is the case with COVID-19.MethodsUsing data from a central registry of electronic health records (the Andalusian Population Health Database), the effect of prior consumption of drugs for other indications previous to the hospitalization with respect to patient outcomes, including survival and lymphocyte progression, was studied on a retrospective cohort of 15,968 individuals, comprising all COVID-19 patients hospitalized in Andalusia between January and November 2020.ResultsCovariate-adjusted hazard ratios and analysis of lymphocyte progression curves support a significant association between consumption of 21 different drugs and better patient survival. Contrarily, one drug, furosemide, displayed a significant increase in patient mortality.ConclusionsIn this study we have taken advantage of the availability of a regional clinical database to study the effect of drugs, which patients were taking for other indications, on their survival. The large size of the database allowed us to control covariates effectively.
WheatLFANet: in-field detection and counting of wheat heads with high-real-time global regression network
Authors: Ye Jianxiong , Yu Zhenghong , Wang Yangxu , Lu Dunlu , Zhou Huabing 
Published: October 2023

AbstractBackgroundDetection and counting of wheat heads are of crucial importance in the field of plant science, as they can be used for crop field management, yield prediction, and phenotype analysis. With the widespread application of computer vision technology in plant science, monitoring of automated high-throughput plant phenotyping platforms has become possible. Currently, many innovative methods and new technologies have been proposed that have made significant progress in the accuracy and robustness of wheat head recognition. Nevertheless, these methods are often built on high-performance computing devices and lack practicality. In resource-limited situations, these methods may not be effectively applied and deployed, thereby failing to meet the needs of practical applications.ResultsIn our recent research on maize tassels, we proposed TasselLFANet, the most advanced neural network for detecting and counting maize tassels. Building on this work, we have now developed a high-real-time lightweight neural network called WheatLFANet for wheat head detection. WheatLFANet features a more compact encoder-decoder structure and an effective multi-dimensional information mapping fusion strategy, allowing it to run efficiently on low-end devices while maintaining high accuracy and practicality. According to the evaluation report on the global wheat head detection dataset, WheatLFANet outperforms other state-of-the-art methods with an average precision AP of 0.900 and an R2value of 0.949 between predicted values and ground truth values. Moreover, it runs significantly faster than all other methods by an order of magnitude (TasselLFANet: FPS: 61).ConclusionsExtensive experiments have shown that WheatLFANet exhibits better generalization ability than other state-of-the-art methods, and achieved a speed increase of an order of magnitude while maintaining accuracy. The success of this study demonstrates the feasibility of achieving real-time, lightweight detection of wheat heads on low-end devices, and also indicates the usefulness of simple yet powerful neural network designs.
THeragnostic utilities for neoplastic DisEases of the rectum by MRI guided radiotherapy (THUNDER 2) phase II trial: interim safety analysis
Authors: Chiloiro Giuditta , Romano Angela , Cusumano Davide , Boldrini Luca , Panza Giulia , Placidi Lorenzo , Meldolesi Elisa , Nardini Matteo , Meffe Guenda , Nicolini Gianluca , Votta Claudio , Indovina Luca , Gambacorta Maria Antonietta 
Published: October 2023

Abstract
Background
The THUNDER-2 phase II single institutional trial investigates the benefits of MRI-guided radiotherapy (MRIgRT) in treating locally advanced rectal cancer (LARC). This study focuses on evaluating the impact of escalating radiation therapy dose in non-responder patients using the Early Tumour Regression Index (ERI) for predicting complete response (CR). The trial’s primary endpoint is to increase the CR rate in non-responders by 10% and assess the feasibility of the delta radiomics-based MRIgRT predictive model. This interim analysis assesses the feasibility and safety of the proposed MRIgRT dose escalation strategy in terms of acute toxicity (gastrointestinal, genitourinary and haematological) and treatment adherence.

Methods
Stage cT2-3, N0-2, or cT4 patients with anal sphincter involvement, N0-2a, M0, but without high-risk features were enrolled. MRIgRT treatment consisted of a standard dose of 55 Gy to the Gross Tumor Volume (GTV) and mesorectum, and 45 Gy to the mesorectum and drainage nodes in 25 fractions with concomitant chemotherapy. 0.35 T MRI was used for simulation imaging and daily alignment. ERI was calculated at the 10th fraction. Non-responders with an ERI above 13.1 received intensified dose escalation from the 11th fraction, resulting in a total dose of 60.1 Gy. Acute toxicity was assessed using the CTCAE v.5 scale.

Results
From March 2021 to November 2022, 33 out of the total number of 63 patients to be enrolled (52.4%) were included, with one withdrawal unrelated to treatment. Sixteen patients (50%) underwent dose escalation. Treatment was well tolerated, with only one patient (3.1%) in the standard treatment group experiencing acute Grade 3 diarrhea, proctitis, and cystitis. No significant differences in toxicity were observed between the two groups (p = 0.5463).

Conclusions
MRIgRT treatment with dose escalation up to 60.1 Gy is well tolerated in LARC patients predicted as non-responders by ERI, confirming the feasibility and safety of this approach. The THUNDER-2 trial’s primary and secondary endpoints will be fully analyzed when all planned patients will be enrolled.
Immediate and longer-term changes in mental health of children with parent–child separation experiences during the COVID-19 pandemic
Authors: Wu Peipei , Wang Shihong , Zhao Xudong , Fang Jiao , Tao Fangbiao , Su Puyu , Wan Yuhui , Sun Ying 
Published: October 2023

Abstract
Background
The psychological impact of the COVID-19 pandemic has been understudied among vulnerable populations. This study aimed to examine the immediate and longer-term changes in the mental health of children with parent–child separation experiences during the COVID-19 pandemic, and identify potential buffering opportunities for mental health.

Methods
This longitudinal cohort study used data from 723 rural Chinese children who provided data before (Oct. 2019) the COVID-19 pandemic and during the following 2 years. Changes in the probability of depressive symptoms, anxiety symptoms, non-suicide self-injurious (NSSI), suicidal ideation, suicide plan, and suicide attempt were tested across four waves using generalized estimating models (GEE).

Results
Compared with children who never experienced parent–child separation, children persistently separated from parents since birth experienced greater deterioration in all mental health in the 2-year follow-up (average change: depressive symptoms: β = 0.59, 95% CI [0.26, 0.93]; anxiety symptoms: β = 0.45, 95% CI [0.10, 0.81]; NSSI: β = 0.66, 95% CI [0.31, 1.01]; suicide ideation: β = 0.67, 95% CI [0.38, 0.96]; suicide plan: β = 0.77, 95% CI [0.38, 1.15]; suicide attempt: β = 1.12, 95% CI [0.63, 1.62]). However, children with childhood separation from their parents but reunited with them during the transition to adolescence showed similar even lower changes to counterparts who never experienced parent–child separation (all ps > 0.05).

Conclusion
These results indicating improvements in supportiveness of the caregiving environment during the transition to adolescence may provide the opportunity to buffer the adverse impact of COVID-19 on mental health. Translating such knowledge to inform intervention and prevention strategies for youths exposed to adversity is a critical goal for the field.
Antidepressants for the prevention of depression following first-episode psychosis (ADEPP): study protocol for a multi-centre, double-blind, randomised controlled trial
Authors: Palmer Edward R. , Griffiths Siân Lowri , Watkins Ben , Weetman Tyler , Ottridge Ryan , Patel Smitaa , Woolley Rebecca , Tearne Sarah , Au Pui , Taylor Eleanor , Sadiq Zara , Al-Janabi Hareth , Major Barnaby , Marriott Charlotte , Husain Nusrat , Katshu Mohammad Zia Ul Haq , Giacco Domenico , Barnes Nicholas M. , Walters James T. R. , Barnes Thomas R. E. , Birchwood Max , Drake Richard , Upthegrove Rachel 
Published: October 2023

Abstract
Background
Depressive episodes are common after first-episode psychosis (FEP), affecting more than 40% of people, adding to individual burden, poor outcomes, and healthcare costs. If the risks of developing depression were lower, this could have a beneficial effect on morbidity and mortality, as well as improving outcomes. Sertraline is a selective serotonin reuptake inhibitor and a common first-line medication for the treatment of depression in adults. It has been shown to be safe when co-prescribed with antipsychotic medication, and there is evidence that it is an effective treatment for depression in established schizophrenia. We present a protocol for a multi-centre, double-blind, randomised, placebo-controlled clinical trial called ADEPP that aims to investigate the efficacy and cost-effectiveness of sertraline in preventing depression after FEP.

Methods
The recruitment target is 452 participants between the ages of 18 and 65 years who are within 12 months of treatment initiation for FEP. Having provided informed consent, participants will be randomised to receive either 50 mg of sertraline daily or matched placebo for 6 months, in addition to treatment as usual. The primary outcome measure will be a comparison of the number of new cases of depression between the treatment and placebo arms over the 6-month intervention phase. Secondary outcomes include suicidal behaviour, anxiety, rates of relapse, functional outcome, quality of life, and resource use.

Discussion
The ADEPP trial will test whether the addition of sertraline following FEP is a clinically useful, acceptable, and cost-effective way of improving outcomes following FEP.

Trial registration
ISRCTN12682719 registration date 24/11/2020.
Preconditioning of the motor network with repetitive navigated transcranial magnetic stimulation (rnTMS) to improve oncological and functional outcome in brain tumor surgery: a study protocol for a randomized, sham-controlled, triple-blind clinical trial
Authors: Engelhardt Melina , Grittner Ulrike , Krieg Sandro , Picht Thomas 
Published: October 2023

Abstract
Background
The extent of resection of glioma is one of the most important predictors of the survival duration of patients after surgery. The presence of eloquent areas within or near a tumor often limits resection, as resection of these areas would result in functional loss and reduced quality of life. The aim of this randomized, triple-blind, sham-controlled study is to investigate the capability of repetitive navigated transcranial magnetic stimulation (rnTMS) over the primary motor cortex to facilitate the functional reorganization of the motor network.

Methods
One hundred forty-eight patients with tumors in movement-relevant areas will be included in this randomized, sham-controlled, bicentric, triple-blind clinical trial. Patients considered at high risk for postoperative motor deficits according to an initial nTMS assessment will receive inhibitory rnTMS at 1 Hz for 30 min followed by a short motor training of 10 min. Stimulation will be applied to the fiber endings of the corticospinal tract closest to the tumor based on individualized tractography. Stimulation will be performed twice daily for each 30 min for 5–28 days depending on the individually available time between study inclusion and surgery. The intervention is controlled by a sham stimulation group (1:1 randomization), where a plastic adapter will be placed on the coil. We expect a comparable or better motor status 3 months postoperatively as measured by the British Medical Research Council (BMRC) score for the affected upper extremity (non-inferiority) and a higher rate of gross total resections (superiority) in the rnTMS compared to the sham group.

Discussion
The generated reorganization of the brain’s areas for motor function should allow a more extensive and safer removal of the tumor while preserving neurological and motor function. This would improve both survival and quality of life of our patients.

Trial registration
DRKS.de DRKS00017232. Registered on 28 January 2020.
High-flow nasal cannula (HFNC) vs continuous positive airway pressure (CPAP) vs nasal intermittent positive pressure ventilation as primary respiratory support in infants of ≥ 32 weeks gestational age (GA): study protocol for a three-arm multi-center randomized controlled trial
Authors: Zhou Rong , Xiong Tao , Tang Jun , Huang Yi , Liu Wenli , Zhu Jun , Chen Chao , Gong Lingyue , Tian Ke , Wang Aoyu , Mu Dezhi 
Published: October 2023

Abstract
Background
Health problems in neonates with gestational age (GA) ≥ 32 weeks remain a major medical concern. Respiratory distress (RD) is one of the common reasons for admission of neonates with GA ≥ 32 weeks. Noninvasive ventilation (NIV) represents a crucial approach to treat RD, and currently, the most used NIV modes in neonatal intensive care unit include high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), and nasal intermittent positive pressure ventilation. Although extensive evidence supports the use of NIPPV in neonates with a GA < 32 weeks, limited data exist regarding its effectiveness in neonates with GA ≥ 32 weeks. Therefore, the aim of this study is to compare the clinical efficacy of HFNC, CPAP, and NIPPV as primary NIV in neonates with GA ≥ 32 weeks who experience RD.

Methods
This trial is designed as an assessor-blinded, three-arm, multi-center, parallel, randomized controlled trial, conducted in neonates ≥ 32 weeks’ GA requiring primary NIV in the first 24 h of life. The neonates will be randomly assigned to one of three groups: HFNC, CPAP or NIPPV group. The effectiveness, safety and comfort of NIV will be evaluated. The primary outcome is the occurrence of treatment failure within 72 h after enrollment. Secondary outcomes include death before discharge, surfactant treatment within 72 h after randomization, duration of both noninvasive and invasive mechanical ventilation, duration of oxygen therapy, bronchopulmonary dysplasia, time to achieve full enteral nutrition, necrotizing enterocolitis, duration of admission, cost of admission, air leak syndrome, nasal trauma, and comfort score.

Discussion
Currently, there is a paucity of data regarding the utilization of NIPPV in neonates with GA ≥ 32 weeks. This study will provide clinical evidence for the development of respiratory treatment strategies in neonates at GA ≥ 32 weeks with RD, with the aim of minimizing the incidence of tracheal intubation and reducing the complications associated with NIV.

Trial registration
Chinese Clinical Trial Registry: ChiCTR2300069192. Registered on March 9, 2023, https://www.chictr.org.cn/showproj.html?proj=171491.
Randomised controlled trial of the Community Navigator programme to reduce loneliness and depression for adults with treatment-resistant depression in secondary community mental health services: trial protocol
Authors: Stefanidou Theodora , Ambler Gareth , Bartl Gergely , Barber Nick , Billings Jo , Bogatsu Tumelo , Carroll Richard , Chipp Beverley , Conneely Maev , Downey Anne-Marie , Evlat Gamze , Hunter Rachael , Le Novere Marie , Lewis Glyn , Mackay Tanya , Marwaha Steven , Matin Zubair , Naughton Georgia , Nekitsing Chandani , O’Sullivan Millie , Pinfold Vanessa , Pan Shengning , Sobers Angela , Thompson Keith J. , Vasikaran Jerusaa , Webber Martin , Johnson Sonia , Lloyd-Evans Brynmor 
Published: October 2023

Abstract
Background
New treatments are needed for people with treatment-resistant depression (TRD), who do not benefit from anti-depressants and many of whom do not recover fully with psychological treatments. The Community Navigator programme was co-produced with service users and practitioners. It is a novel social intervention which aims to reduce loneliness and thus improve health outcomes for people with TRD. Participants receive up to 10 individual meetings with a Community Navigator, who helps them to map their social world and set and enact goals to enhance their social connections and reduce loneliness. Participants may also access group meet-ups with others in the programme every 2 months, and may be offered modest financial support to enable activities to support social connections.

Methods
A researcher-blind, multi-site, 1:1 randomised controlled trial with N = 306 participants will test the effectiveness of the Community Navigator programme for people with TRD in secondary community mental health teams (CMHTs). Our primary hypothesis is that people who are offered the Community Navigator programme as an addition to usual CMHT care will be less depressed, assessed using the PHQ-9 self-report measure, at 8-month, end-of-treatment follow-up, compared to a control group receiving usual CMHT care and a booklet with information about local social groups and activities. We will follow participants up at end-of-treatment and at 14 months, 6 months after end-of-treatment follow-up. Secondary outcomes include the following: loneliness, anxiety, personal recovery, self-efficacy, social network, social identities. We will collect data about health-related quality of life and service use to investigate the cost-effectiveness of the Community Navigator programme.

Discussion
This trial will provide definitive evidence about the effectiveness and cost-effectiveness of the Community Navigator programme and whether it can be recommended for use in practice. The trial is due to finish in August 2025.

Trial registration
Prospectively registered on 8th July 2022 at: ISRCTN13205972.
Digital CBTI hubs as a treatment augmentation strategy in military clinics: study protocol for a pragmatic randomized clinical trial
Authors: Germain Anne , Wolfson Megan , Brock Matthew S. , O’Reilly Brian , Hearn Hunter , Knowles Shelley , Mysliwiec Vincent , Wallace Meredith L. 
Published: October 2023

Abstract
Background
Chronic insomnia is the most prevalent sleep disorder among military service members, and it compromises readiness, performance, and physical and mental health. Cognitive behavioral treatment for insomnia (CBTI) is the standard of care for the treatment of insomnia recommended by the VA/DoD Clinical Practice Guideline, the American Academy of Sleep Medicine, and the American College of Physicians. CBTI is highly effective but has limited scalability. It is often unavailable in clinical settings where service members receive sleep care. Digital technologies offer unique opportunities to scale and broaden the geographic reach of CBTI services and support increased patient access and engagement in behavioral sleep care. This study aims to evaluate the impact and acceptability of digital CBTI hubs to augment military treatment facilities’ capabilities in behavioral sleep medicine.

Methods
This is a multi-site, non-inferiority randomized clinical trial designed to compare the effects of in-person (face-to-face or virtual) insomnia care as usual at three military sleep clinics versus CBTI delivered remotely and asynchronously through digital CBTI hubs. Digital CBTI hubs are led by licensed, certified clinicians who use NOCTEM’s® evidence-based clinical decision support platform COAST™ (Clinician Operated Assistive Sleep Technology). Changes in insomnia severity and daytime symptoms of depression and anxiety will be compared at baseline, at 6–8 weeks, and at 3-month follow-up. Patient satisfaction with insomnia care as usual versus digital CBTI hubs will also be examined. We hypothesize that digital CBTI hubs will be non-inferior to insomnia care as usual for improvements in insomnia and daytime symptoms as well as patient satisfaction with insomnia care.

Discussion
Digital technology has a high potential to scale CBTI accessibility and delivery options required to meet the insomnia care needs of military service members. Digital CBTI hubs using COAST offer a novel approach to broaden service members’ access to CBTI and to serve as an augmentation strategy for existing sleep services at military treatment facilities. The pragmatic approach leveraging technology in this trial has the potential to rapidly inform clinical practice within the Defense Health Agency as well as other healthcare systems.

Trial registration
ClinicalTrials.gov NCT05490550. Registered on 14 July 2023.
Alternative ground covers and strip-tilling in CBD hemp production
Authors: Osorio Erika , Fisher Benjamin , Foster Matt , Voigt Brian , von Wettberg Eric J. B. 
Published: October 2023

Abstract
Objective
Little research has been done on managing soil health for large-scale, outdoor hemp production, contributing to the possible overuse of black plastic for weed suppression. Our experiment aimed to understand the performance of alternative ground covers including forage crops and hay as well as a less disruptive tilling method called strip-tilling compared to black plastic.

Results
Yield and soil health data were taken from three experimental plantings from two different outdoor CBD hemp farms in Vermont, USA. We find that hay may be a competitive alternative to black plastic in terms of producing heavier plants. Our research also found that clover seed and hay are both more cost-effective options than black plastic which may sway some farmers to adopt these alternative ground cover options.