bluuebunny/crossref_metadata_2025_split huggingface dataset:
Schema therapy versus treatment as usual for outpatients with difficult-to-treat depression: study protocol for a parallel group randomized clinical trial (DEPRE-ST)
Authors: Arendt Ida-Marie T. P. , Gondan Matthias , Juul Sophie , Hastrup Lene Halling , Hjorthøj Carsten , Bach Bo , Videbech Poul , Jørgensen Martin Balslev , Moeller Stine Bjerrum 
Published: April 2024

Abstract
Background
About one third of patients with depression are in a condition that can be termed as “difficult-to-treat”. Some evidence suggests that difficult-to-treat depression is associated with a higher frequency of childhood trauma and comorbid personality disorders or accentuated features. However, the condition is understudied, and the effects of psychotherapy for difficult-to-treat depression are currently uncertain. The aim of this trial is to investigate the beneficial and harmful effects of 30 sessions of individual schema therapy versus treatment as usual for difficult-to-treat depression in the Danish secondary, public mental health sector.

Methods
In this randomized, multi-centre, parallel-group, superiority clinical trial, 129 outpatients with difficult-to-treat depression will be randomized (1:1) to 30 sessions of individual schema therapy or treatment as usual; in this context mainly group-based, short-term cognitive behaviour or psychodynamic therapy. The primary outcome is the change from baseline in depressive symptoms 12 months after randomization, measured on the observer-rated 6-item Hamilton Rating Scale for Depression. The secondary outcomes are health-related quality of life assessed with the European Quality of Life 5 Dimensions 5 Level Version, functional impairment assessed with the Work and Social Adjustment Scale, psychological wellbeing assessed with the WHO-5 Well-being Index, and negative effects of treatment assessed with the Negative Effects Questionnaire. Exploratory outcomes are improvement on patient self-defined outcomes, personal recovery, anxiety symptoms, anger reactions, metacognitive beliefs about anger, and perseverative negative thinking. Outcomes will be assessed at 6, 12, and 24 months after randomization; the 12-month time-point being the primary time-point of interest. Outcome assessors performing the depression-rating, data managers, statisticians, the data safety and monitoring committee, and conclusion makers for the outcome article will be blinded to treatment allocation and results. To assess cost-effectiveness of the intervention, a health economic analysis will be performed.

Discussion
This trial will provide evidence on the beneficial and harmful effects, as well as the cost-effectiveness of schema therapy versus treatment as usual for outpatients with difficult-to-treat depression. The results can potentially improve treatment for a large and understudied patient group.

Trial registration
ClinicalTrials.gov NCT05833087. Registered on 15th April 2023 (approved without prompts for revision on 27th April 2023).
Look4LTRs: a Long terminal repeat retrotransposon detection tool capable of cross species studies and discovering recently nested repeats
Authors: Garza Anthony B. , Lerat Emmanuelle , Girgis Hani Z. 
Published: April 2024

AbstractPlant genomes include large numbers of transposable elements. One particular type of these elements is flanked by two Long Terminal Repeats (LTRs) and can translocate using RNA. Such elements are known as LTR-retrotransposons; they are the most abundant type of transposons in plant genomes. They have many important functions involving gene regulation and the rise of new genes and pseudo genes in response to severe stress. Additionally, LTR-retrotransposons have several applications in biotechnology. Due to the abundance and the importance of LTR-retrotransposons, multiple computational tools have been developed for their detection. However, none of these tools take advantages of the availability of related genomes; they process one chromosome at a time. Further, recently nested LTR-retrotransposons (multiple elements of the same family are inserted into each other) cannot be annotated accurately — or cannot be annotated at all — by the currently available tools. Motivated to overcome these two limitations, we built Look4LTRs, which can annotate LTR-retrotransposons in multiple related genomes simultaneously and discover recently nested elements. The methodology of Look4LTRs depends on techniques imported from the signal-processing field, graph algorithms, and machine learning with a minimal use of alignment algorithms. Four plant genomes were used in developing Look4LTRs and eight plant genomes for evaluating it in contrast to three related tools. Look4LTRs is the fastest while maintaining better or comparable F1 scores (the harmonic average of recall and precision) to those obtained by the other tools. Our results demonstrate the added benefit of annotating LTR-retrotransposons in multiple related genomes simultaneously and the ability to discover recently nested elements. Expert human manual examination of six elements — not included in the ground truth — revealed that three elements belong to known families and two elements are likely from new families. With respect to examining recently nested LTR-retrotransposons, three out of five were confirmed to be valid elements. Look4LTRs — with its speed, accuracy, and novel features — represents a true advancement in the annotation of LTR-retrotransposons, opening the door to many studies focused on understanding their functions in plants.
Effectiveness and safety of manual therapy when compared with oral pain medications in patients with neck pain: a systematic review and meta-analysis
Authors: Makin Joshua , Watson Lauren , Pouliopoulou Dimitra V , Laframboise Taylor , Gangloff Bradley , Sidhu Ravinder , Sadi Jackie , Parikh Pulak , Gross Anita , Langevin Pierre , Gillis Heather , Bobos Pavlos 
Published: April 2024

Abstract
Background
This systematic review and meta-analysis seeks to investigate the effectiveness and safety of manual therapy (MT) interventions compared to oral pain medication in the management of neck pain.

Methods
We searched from inception to March 2023, in Cochrane Central Register of Controller Trials (CENTRAL), MEDLINE, EMBASE, Allied and Complementary Medicine (AMED) and Cumulative Index to Nursing and Allied Health Literature (CINAHL; EBSCO) for randomized controlled trials that examined the effect of manual therapy interventions for neck pain when compared to medication in adults with self-reported neck pain, irrespective of radicular findings, specific cause, and associated cervicogenic headaches. We used the Cochrane Risk of Bias 2 tool to assess the potential risk of bias in the included studies, and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach to grade the quality of the evidence.

Results
Nine trials (779 participants) were included in the meta-analysis. We found low certainty of evidence that MT interventions may be more effective than oral pain medication in pain reduction in the short-term (Standardized Mean Difference: -0.39; 95% CI -0.66 to -0.11; 8 trials, 676 participants), and moderate certainty of evidence that MT interventions may be more effective than oral pain medication in pain reduction in the long-term (Standardized Mean Difference: − 0.36; 95% CI − 0.55 to − 0.17; 6 trials, 567 participants). We found low certainty evidence that the risk of adverse events may be lower for patients that received MT compared to the ones that received oral pain medication (Risk Ratio: 0.59; 95% CI 0.43 to 0.79; 5 trials, 426 participants).

Conclusions
MT may be more effective for people with neck pain in both short and long-term with a better safety profile regarding adverse events when compared to patients receiving oral pain medications. However, we advise caution when interpreting our safety results due to the different level of reporting strategies in place for MT and medication-induced adverse events. Future MT trials should create and adhere to strict reporting strategies with regards to adverse events to help gain a better understanding on the nature of potential MT-induced adverse events and to ensure patient safety.

Trial registration
PROSPERO registration number: CRD42023421147.
GLUT1-mediated microglial proinflammatory activation contributes to the development of stress-induced spatial learning and memory dysfunction in mice
Authors: Wang Xue , Wu Yuhan , Tian Yingrui , Hu Hui , Zhao Yun , Xue Binghua , Sun Zhaowei , Wei Aijun , Xie Fang , Qian Ling-Jia 
Published: April 2024

Abstract
Background
Stress is a recognized risk factor for cognitive decline, which triggers neuroinflammation involving microglial activation. However, the specific mechanism for microglial activation under stress and affects learning and memory remains unclear.

Methods
The chronic stress mouse model was utilized to explore the relationship between microglial activation and spatial memory impairment. The effect of hippocampal hyperglycemia on microglial activation was evaluated through hippocampal glucose-infusion and the incubation of BV2 cells with high glucose. The gain-and loss-of-function experiments were conducted to investigate the role of GLUT1 in microglial proinflammatory activation. An adeno-associated virus (AAV) was employed to specifically knockdown of GLUT1 in hippocampal microglia to assess its impact on stressed-mice.

Results
Herein, we found that chronic stress induced remarkable hippocampal microglial proinflammatory activation and neuroinflammation, which were involved in the development of stress-related spatial learning and memory impairment. Mechanistically, elevated hippocampal glucose level post-stress was revealed to be a key regulator of proinflammatory microglial activation via specifically increasing the expression of microglial GLUT1. GLUT1 overexpression promoted microglial proinflammatory phenotype while inhibiting GLUT1 function mitigated this effect under high glucose. Furthermore, specific downregulation of hippocampal microglial GLUT1 in stressed-mice relieved microglial proinflammatory activation, neuroinflammation, and spatial learning and memory injury. Finally, the NF-κB signaling pathway was demonstrated to be involved in the regulatory effect of GLUT1 on microglia.

Conclusions
We demonstrate that elevated glucose and GLUT1 expression induce microglia proinflammatory activation, contributing to stress-associated spatial memory dysfunction. These findings highlight significant interplay between metabolism and inflammation, presenting a possible therapeutic target for stress-related cognitive disorders.
The chain of survival and rehabilitation for sepsis: concepts and proposals for healthcare trajectory optimization
Authors: Jouffroy Romain , Djossou Félix , Neviere Rémi , Jaber Samir , Vivien Benoît , Heming Nicholas , Gueye Papa 
Published: April 2024

SummaryThis article describes the structures and processes involved in healthcare delivery for sepsis, from the prehospital setting until rehabilitation. Quality improvement initiatives in sepsis may reduce both morbidity and mortality. Positive outcomes are more likely when the following steps are optimized: early recognition, severity assessment, prehospital emergency medical system activation when available, early therapy (antimicrobials and hemodynamic optimization), early orientation to an adequate facility (emergency room, operating theater or intensive care unit), in-hospital organ failure resuscitation associated with source control, and finally a comprehensive rehabilitation program. Such a trajectory of care dedicated to sepsis amounts to a chain of survival and rehabilitation for sepsis. Implementation of this chain of survival and rehabilitation for sepsis requires full interconnection between each link. To date, despite regular international recommendations updates, the adherence to sepsis guidelines remains low leading to a considerable burden of the disease. Developing and optimizing such an integrated network could significantly reduce sepsis related mortality and morbidity.
Multifactorial analysis of willingness to undergo subcutaneous allergen immunotherapy in pediatric patients
Authors: Ding Bo , Zhong Jie , Jiang Chun , Ma Tian , Shen Qiuzhi , Lu Yanming 
Published: April 2024

Objective: To explore factors influencing the acceptance of allergen immunotherapy (AIT) for the treatment of allergic respiratory diseases by pediatric patients and their families.
Methods: A total of 406 children (210 males and 196 females) attending the pediatric outpatient clinics and wards of the Renji Hospital, Shanghai Jiao Tong University School of Medicine from June 2020 to April 2022. Those who met the criteria for the AIT treatment, were included in the survey. An online 20-item questionnaire was developed. Data on patient’s general characteristics, allergic disease status, family history of allergies, general family information, parental knowledge of allergic diseases, and whether the AIT treatment was recommended by a physician, were collected. The patients were divided into two groups according to their willingness to receive AIT: a reluctant or neutral group (n = 182), and a willing group (n = 224). A univariate analysis of the willingness to undergo AIT was done to detect parameters that significantly differed between the groups, and the identified factors were used as independent variables in the multifactorial logistic regression analysis.
Results: The severity of allergic disease, presence of drug allergy, occurrence of severe allergic reactions, mother’s education, distance from home to the hospital, parental knowledge of allergic diseases, and whether the doctor recommended AIT were all statistically different between the groups (p < 0.05). Multifactorial logistic regression analysis showed that the degree of allergic rhinitis (AR), or asthma (AS), parental knowledge of allergic diseases, and doctor’s recommendation of AIT were the factors that influenced the willingness of pediatric patients to receive AIT.
Conclusions: The severity of AR and AS, parental knowledge of allergic diseases, and doctor’s recommendation influenced the willingness of pediatric patients to receive AIT.
doi: https://doi.org/10.12669/pjms.40.5.8581
How to cite this: Ding B, Zhong J, Jiang C, Ma T, Shen Q, Lu Y. Measurement of Service Quality Gaps in Dental Services using SERVQUAL in Public Hospitals of Rawalpindi. Pak J Med Sci. 2024;40(5):820-828. doi: https://doi.org/10.12669/pjms.40.5.8581
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
‘Not finding causal effect’ is not ‘finding no causal effect’ of school closure on COVID-19
Authors: Endo Akira 
Published: April 2024

In a paper recently published in Nature Medicine, Fukumoto et al. tried to assess the government-led school closure policy during the early phase of the COVID-19 pandemic in Japan. They compared the reported incidence rates between municipalities that had and had not implemented school closure in selected periods from March–May 2020, where they matched for various potential confounders, and claimed that there was no causal effect on the incidence rates of COVID-19. However, the effective sample size (ESS) of their dataset had been substantially reduced in the process of matching due to imbalanced covariates between the treatment (i.e. with closure) and control (without closure) municipalities, which led to the wide uncertainty in the estimates. Despite the study title starting with “No causal effect of school closures”, their results are insufficient to exclude the possibility of a strong mitigating effect of school closure on incidence of COVID-19. In this replication/reanalysis study, we showed that the confidence intervals of the effect estimates from Fukumoto et al. included a 100% relative reduction in COVID-19 incidence. Simulations of a hypothetical 50% or 80% mitigating effect hardly yielded statistical significance with the same study design and sample size. We also showed that matching of variables that had large influence on propensity scores (e.g. prefecture dummy variables) may have been incomplete.
Robust-to-Dynamics Optimization
Authors: Ahmadi Amir Ali , Günlük Oktay 
Published: April 2024

A robust-to-dynamics optimization (RDO) problem is an optimization problem specified by two pieces of input: (i) a mathematical program (an objective function [Formula: see text] and a feasible set [Formula: see text]) and (ii) a dynamical system (a map [Formula: see text]). Its goal is to minimize f over the set [Formula: see text] of initial conditions that forever remain in [Formula: see text] under g. The focus of this paper is on the case where the mathematical program is a linear program and where the dynamical system is either a known linear map or an uncertain linear map that can change over time. In both cases, we study a converging sequence of polyhedral outer approximations and (lifted) spectrahedral inner approximations to [Formula: see text]. Our inner approximations are optimized with respect to the objective function f, and their semidefinite characterization—which has a semidefinite constraint of fixed size—is obtained by applying polar duality to convex sets that are invariant under (multiple) linear maps. We characterize three barriers that can stop convergence of the outer approximations to [Formula: see text] from being finite. We prove that once these barriers are removed, our inner and outer approximating procedures find an optimal solution and a certificate of optimality for the RDO problem in a finite number of steps. Moreover, in the case where the dynamics are linear, we show that this phenomenon occurs in a number of steps that can be computed in time polynomial in the bit size of the input data. Our analysis also leads to a polynomial-time algorithm for RDO instances where the spectral radius of the linear map is bounded above by any constant less than one. Finally, in our concluding section, we propose a broader research agenda for studying optimization problems with dynamical systems constraints, of which RDO is a special case. Funding: O. Günlük was partially supported by the Office of Naval Research [Grant N00014-21-1-2575]. This work was partially funded by the Alfred P. Sloan Foundation, the Air Force Office of Scientific Research, Defense Advanced Research Projects Agency [Young Faculty Award], the National Science Foundation [Faculty Early Career Development Program Award], and Google [Faculty Award].
Disseminated melioidosis presenting as sepsis, neurological melioidosis, liver and prostate abscess in United Arab Emirates
Authors: Maria Hasani Maria Hasani , Sadia Rounak Shriya Sadia Rounak Shriya , Thahira Mariyam , Haque Saima , Khan Saima Liyakat , Azza Shaloob Azza Shaloob , Sara Osman Sara Osman 
Published: April 2024

Background: Melioidosis is an infection caused by Burkholderia pseudomallei, a Gram-negative bacterium. It is a disease endemic to Southeast Asia and northern Australia although its global incidence has been rising. It most commonly infects people with certain identified risk factors such as diabetes, alcoholism, thalassemia, and underlying chronic disease involving lungs, kidney and liver. This bacterium is capable of producing a wide array of clinical manifestations ranging from asymptomatic disease to localised infections such as in the lung, bone or skin to disseminated infection. Case description: This is a case, from United Arab Emirates, of a 40-year-old male recently diagnosed with diabetes who presented with multiple abscesses and was eventually diagnosed with disseminated melioidosis. He was treated successfully with antibiotics and drainage of abscesses. Conclusion: In non-endemic regions, melioidosis can be easily missed in common diagnostic approaches. This gap of awareness could delay the diagnosis and allow further deterioration of the patient due to complications. Thus, case reports like this can enlighten internists about changing incidences and complexity of clinical presentations, thus preparing them to better handle such patients in the future.
Group B Streptococcus meningitis in an adult woman with type 2 diabetes and ethmoid roof defect. Impact on “frontal” cognitive functions
Authors: Vicinanza Roberto , Miscetti Alice , Magistrato Cesare , Castiglione Melina , Frizza Alessandro 
Published: April 2024

Background: Community-acquired bacterial meningitis in adults represents one of the most severe infectious diseases worldwide with potentially life-threatening medical complications. Several infectious agents can cause acute meningitis. Although group B Streptococcus is more prevalent in newborns, infection can also lead to meningitis in older adults, particularly those with underlying health issues. Case Description: A 53-year-old woman with a body mass index of 28.7 kg/m2, type 2 diabetes mellitus, and dyslipidaemia presented to the emergency department of Santa Maria della Stella Hospital (Orvieto, Italy) with confusion, low-grade fever, echolalia, and hyperglycaemia. Computed tomography scans of the brain revealed a hypodensity in the left anterior frontal lobe and an osteodural defect of the rhinobase. Meningitis was suspected and empiric broad-spectrum antibiotic therapy with corticosteroids and insulin were administered while the results of the cerebrospinal fluid analysis confirmed the diagnosis of group B Streptococcus meningitis. Repeat imaging at 48 hours revealed enlargement of the hypodense lesion. The frontal assessment battery indicated deficits in executive functions. Prompt treatment led to rapid clinical improvement. Following the restoration of euglycemic status and hemodynamic stabilization, a follow-up magnetic resonance imaging confirmed the ischaemic lesion and showed cerebrospinal fluid in the sella turcica. The patient was then transferred to neurorehabilitation. Conclusions: The complex interactions among multiple risk factors resulted in an atypical clinical case of group B Streptococcus meningitis, which was promptly treated with empiric antibiotic therapy to mitigate neurocognitive deficits.
Thoracic spine infection caused by Pseudomonas fluorescens: A case report and review of literature
Authors: Li Liang , Zhang Bao-Hua , Cao Jin-Feng , Zhang Li-Jin , Guo Ling-Ling 
Published: April 2024

BACKGROUND
The clinical incidence of spinal infection is gradually increasing, and its onset is insidious, easily leading to missed diagnosis and misdiagnosis, which may lead to serious complications such as nervous system dysfunction, spinal instability and/or deformity, and cause a huge burden on society and families. Early identification of the causative agent and precision medicine will greatly reduce the suffering of patients. At present, the main pathogenic bacteria that cause spinal infection are Staphylococcus aureus , Streptococcus, Pneumococcus, Escherichia coli , and Klebsiella. There are no reports of spinal infection caused by Pseudomonas fluorescens .
CASE SUMMARY
We report a 32-year-old female patient with spinal infection. She presented with flank pain, initially thought to be bone metastases or bone tuberculosis, and had a family background of tumors. Her clinical features and changes in imaging and laboratory tests led to the suspicion of thoracic spine infection. Histopathology of the lesion showed inflammation, tissue culture of the lesion was negative several times, and the possible pathogen - Pseudomonas fluorescens was found after gene sequencing of the lesion. The patient recovered completely after a full course of antibiotic treatment.
CONCLUSION
This report increases the range of pathogens involved in spinal infections, highlights the unique advantages of gene sequencing technology in difficult-to-diagnose diseases, and validates conservative treatment with a full course of antibiotics for spinal infections without complications.