bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histamine H3 receptor inverse agonists/antagonists influence intra-regional cortical activity and inter-regional synchronization during resting state: an exploratory cortex-wide imaging study in mice
Authors: Kaita Sentaro , Morishita Yoshikazu , Kobayashi Kenta , Nomura Hiroshi 
Published: November 2024

AbstractThe histaminergic system plays a key role in modulating learning and memory, wakefulness, and energy balance. Histamine H3 receptors constitutively inhibit the synthesis and release of histamine and other neurotransmitters. Therefore, H3 receptor inverse agonists/antagonists increase the synthesis and release of these neurotransmitters, enhancing cognitive functions, including memory consolidation and retrieval. Spontaneous neural activity across the cerebral cortex is essential for cognitive function, including memory consolidation. Abnormal spontaneous activity has, in fact, been associated with cognitive dysfunctions and psychiatric disorders. Given the cognitive improvement achieved with the use of H3 receptor inverse agonists/antagonists, we examined the effects of two inverse agonists/antagonists – thioperamide and pitolisant – on spontaneous cortical activity, using in vivo wide-field Ca2+ imaging. Changes in cortical activity, across multiple cortical regions and in inter-regional connectivity, from pre- to post-administration were evaluated using a linear support vector machine decoder. Thioperamide and pitolisant both modified the amplitude distribution of calcium events across multiple cortical regions, including a reduction in the frequency of low-amplitude calcium events in the somatosensory cortex. Graph theory analysis revealed increases in centrality measures in the somatosensory cortex with the use of both thioperamide and pitolisant, indicative of their importance in the organization of cortical networks. These findings indicate that H3 receptor inverse agonists/antagonists influence intra-regional cortical activity and inter-regional synchronization of activity in the cerebral cortex during the resting state.
Modification of the COPSOQ adapted for the IT sector – a journey of validation and insight for futures research, prognosis global risks
Authors: Gren Maria 
Published: November 2024

AbstractThis study presents the validation process of the Copenhagen Psychosocial Questionnaire (COPSOQ) adapted for the IT sector, focusing on its reliability and validity within a German-speaking context (IT professionals in Austria). The COPSOQ is an established instrument for assessing psychosocial work environment factors. While previous research has highlighted its applicability across various cultural settings, this paper delves into its psychometric properties through exploratory factor analysis (EFA) using a sample of 200 IT professionals. The survey, conducted online, adapted the German COPSOQ including additional items relevant to the IT work environment, with some items being removed for greater efficiency and specificity. The analysis yielded seven factors, explaining 52.2% of the variance and reflecting key psychosocial dimensions: job identification, influencing factors, life satisfaction, self-determination, social support, life-dominant balance, and job concerns. The paper argues for the removal of certain items with loadings below .40 to enhance the questionnaire's economy and efficiency. Furthermore, it suggests that the refined COPSOQ could be a more effective tool for assessing work stress among IT workers, potentially leading to better-informed workplace interventions and improved prognosis for employee well-being. This research underscores the importance of adapting psychosocial assessment tools to specific industry contexts, providing a robust foundation for future studies on the work environment and its impact on quality of life and job satisfaction among IT professionals, and addressing global risks associated with workplace stress. Additionally, the paper ties these findings with broader global risks, such as technology-induced stress and the future of work, which are critical for developing resilient organizational frameworks.
Stress drives premature hive exiting behavior that leads to death in young honey bee (Apis mellifera) workers
Authors: Ellis Jordan Twombly , Rangel Juliana 
Published: November 2024

Abstract
Background
The Western honey bee, Apis mellifera, is an economically important pollinator, as well as a tractable species for studying the behavioral intricacies of eusociality. Honey bees are currently being challenged by multiple biotic and environmental stressors, many of which act concomitantly to affect colony health and productivity. For instance, developmental stress can lead workers to become precocious foragers and to leave the hive prematurely. Precocious foragers have decreased flight time and lower foraging efficiency, which can ultimately lower colony productivity and even lead to colony collapse.

Materials and methods
In this study, we tested the hypothesis that stress during pupal development can cause young workers to exit the hive prematurely before they are physically able to fly. This premature exiting behavior results in death outside the hive soon thereafter. To determine how various stressors may lead bees to perform this behavior, we subjected workers during the last pupal stage to either cold stress (26 °C for 24 h), heat stress (39 °C for 24 h), or Varroa destructor mite parasitization, and compared the rate of premature hive exits between stressed bees and their respective control counterparts. Upon emergence, we individually tagged focal bees in all treatment groups and introduced them to a common observation hive. We then followed tagged bees over time and monitored their survivorship, as well as their likelihood of performing the premature hive exiting behavior. We also dissected the hypopharyngeal glands of all treatment and control bees sampled.

Results
We found that significantly more bees in all three treatment groups exited the hive prematurely compared to their control counterparts. Bees in all treatment groups also had significantly smaller hypopharyngeal glands than control bees.

Conclusions
Our results suggest that premature hive exiting behavior is driven by stress and is potentially a form of accelerated age polyethism that leads to premature death.
Distribution of Candida species isolated from people living with human immunodeficiency virus with oropharyngeal and oral candidiasis in Africa in the era of universal test and treat policy: a systematic review and meta-analysis
Authors: Musinguzi Benson , Obuku Ekwaro A. , Mwesigwa Alex , Migisha Richard , Kinengyere Alison Annet , Ndagire Regina , Baguma Andrew , Okek Erick Jacob , Olum Ronald , Itabangi Herbert , Mboowa Gerald , Sande Obondo James , Achan Beatrice 
Published: November 2024

Abstract
Background
The introduction of antiretroviral therapy (ART) and the implementation of the human immunodeficiency virus (HIV) universal test and treat (UTT) policy have led to a decline in the incidence of opportunistic infections. However, oropharyngeal and oral candidiasis remain prevalent and continue to pose challenges among people living with human immunodeficiency virus (PLHIV) in Africa, indicating the need for a better understanding of the distribution of Candida species responsible for these infections. This systematic review and meta-analysis aimed to determine the distribution of Candida species isolated from PLHIV with oropharyngeal and oral candidiasis in Africa in the era of UTT policy.

Methods
The review followed the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. A comprehensive search was conducted to identify eligible studies to be included in the meta-analysis and analysed using a random effects model in STATA version 17.
The risk of bias was assessed using the Joanna Briggs Institute quality assessment tool.

Results
Fourteen studies with 4281 participants were included in the review. Overall, 2095 Candida isolates were reported, 78.7% (1650/2095) of which were C. albicans, 19.6% (410/2095), non-albicans Candida (NAC), and 1.7% (35/2095) could not be identified to the Candida specific species level. The most prevalent NAC species were C. glabrata (26.3%), followed by C. tropicalis (24.9%), C. krusei (15.6%), C. parapsilosis (11%), and C. dubliniensis (6.3%). The pooled prevalence of oropharyngeal and oral candidiasis was 48% (95% CI 34–62%). The prevalence of oropharyngeal candidiasis was higher in the pre-UTT era, at 56% (95% CI 40–72%, p < 0.001), than in the post-UTT era, at 34% (95% CI 10–67%, p < 0.001). The risk of bias assessment revealed that 71.4% (10/14) of the included studies had a low risk of bias and that 28.6% (4/14) had a moderate risk of bias.

Conclusions
While C. albicans remain, the predominant species causing oropharyngeal and oral candidiasis among PLHIV in Africa, NAC species also contribute significantly to the infection burden. Despite ART and UTT policies, oropharyngeal candidiasis remains prevalent, emphasizing the need for targeted interventions.
Cell fusion dynamics: mechanisms of multinucleation in osteoclasts and macrophages
Authors: Sabe Hideaki , Yahara Yasuhito , Ishii Masaru 
Published: November 2024

AbstractCell–cell fusion is a vital biological process where the membranes of two or more cells merge to form a syncytium. This phenomenon is critical in various physiological and pathological contexts, including embryonic development, tissue repair, immune responses, and the progression of several diseases. Osteoclasts, which are cells from the monocyte/macrophage lineage responsible for bone resorption, have enhanced functionality due to cell fusion. Additionally, other multinucleated giant cells (MGCs) also arise from the fusion of monocytes and macrophages, typically during chronic inflammation and reactions to foreign materials such as prostheses or medical devices. Foreign body giant cells (FBGCs) and Langhans giant cells (LGCs) emerge only under pathological conditions and are involved in phagocytosis, antigen presentation, and the secretion of inflammatory mediators. This review provides a comprehensive overview of the mechanisms underlying the formation of multinucleated cells, with a particular emphasis on macrophages and osteoclasts. Elucidating the intracellular structures, signaling cascades, and fusion-mediating proteins involved in cell–cell fusion enhances our understanding of this fundamental biological process and helps identify potential therapeutic targets for disorders mediated by cell fusion.
A deep learning based automatic two-dimensional digital templating model for total knee arthroplasty
Authors: Park Jaeseok , Kim Sung Eun , Kim Back , Lee Sanggyu , Lee Jae-Jun , Ro Du Hyun 
Published: November 2024

Abstract
Background
Preoperative templating is an important step for total knee arthroplasty (TKA), facilitating hospital personnel in the anticipation and preparation of necessary surgical resources. Despite its importance, this process currently lacks automation. This study aimed to develop an artificial intelligence (AI) model to automate implant size prediction.

Methods
A total of 13,281 (2938 anteroposterior, 10,343 lateral) knee radiographs obtained from the authors’ institute were utilized for model training, with 2302 (1034 anteroposterior, 1268 lateral) images set apart for validation and testing. The templating AI model integrates a pipeline composed of multiple steps for automated implant size estimation. To predict implant size, anterioposterior (AP) and lateral radiograph predictions were merged, selecting the smaller of the predicted sizes to prevent implant overhang. The model’s size predictions were validated with 81 real TKA data set apart from the training data, and its accuracy was compared to that of manual templating by an orthopedic specialist. Predictions matching the actual implanted sizes were labeled “exact” and those within one size, “accurate.” The influence of patient characteristics on the model’s prediction accuracy was also analyzed. The measurement time elapsed for implant sizing was recorded for both the AI model and the orthopedic specialist. Implant position predicted by the model was validated by comparing insert locations with postoperative images.

Results
Compared with data from 81 actual TKA procedures, the model provided exact predictions for 39.5% of femoral and 43.2% of tibial components. Allowing a one-size margin of error, 88.9% of predictions were deemed “accurate” for both components. Interobserver reliability (Cohen’s kappa) were 0.60 and 0.70 for femoral and tibial implants, respectively, both classified as “substantial.” The orthopedic specialist produced results accurate within one-size margin of error in 95.1% and 100% of cases for femoral and tibial components, respectively. Interobserver reliability between the orthopedic specialist and ground truth was 0.76 and 0.8 for femoral and tibial components, respectively. The measurement time per case was 48.7 s for the AI model, compared with 97.5 s for the orthopedic specialist. Compared with postoperative radiographs, predicted implant position had an error of less than 4 mm on average.

Conclusions
An AI-based templating tool for TKA was successfully developed, demonstrating satisfactory accuracy and efficiency. Its application could significantly reduce the clinical workload in TKA preparation.
Ibrutinib in Early-Stage Chronic Lymphocytic Leukemia: The Randomized, Placebo-Controlled, Double-Blind, Phase III CLL12 Trial
Authors: Langerbeins Petra , Robrecht Sandra , Nieper Pascal , Cramer Paula , Fürstenau Moritz , Al-Sawaf Othman , Simon Florian , Fink Anna-Maria , Kreuzer Karl-Anton , Vehling-Kaiser Ursula , Tausch Eugen , Schneider Christof , Müller Lothar , Eckart Michael Josef , Schlag Rudolf , Freier Werner , Gaska Tobias , Balser Christina , Reiser Marcel , Stauch Martina , Zahn Mark-Oliver , Dörfel Steffen , Staib Peter , Behlendorf Timo , Hensel Manfred , Hebart Holger , Klaproth Holger , Block Andreas , Liersch Rüdiger , Hauch Ulrich , Heinrich Bernhard , Wendtner Clemens-Martin , Fischer Kirsten , Stilgenbauer Stephan , Eichhorst Barbara , Hallek Michael 
Published: November 2024

PURPOSE
The CLL12 trial reassesses the watch-and-wait consensus for early-stage chronic lymphocytic leukemia (CLL) in the context of targeted therapies.

METHODS
The German CLL Study Group conducted a randomized, double-blind, placebo-controlled phase III trial with 363 patients with asymptomatic, treatment-naïve Binet stage A CLL at increased risk of progression to receive ibrutinib (n = 182) at a daily dose of 420 mg or placebo (n = 181). Additionally, 152 low-risk patients were allocated to the watch-and-wait group. The final analysis included event-free survival, progression-free survival, time to next treatment, overall survival, and safety assessments.

RESULTS

Ibrutinib significantly delayed progression to symptomatic disease (
P
< .001; hazard ratio, 0.276 [95% CI, 0.188 to 0.407]), but no survival benefit was observed with 26 death cases (
P
= .562) at a median observation time of 69.3 months. Five-year survival rates were excellent: 93.3% (95% CI, 89.3 to 97.3) in the ibrutinib group, 93.6% (95% CI, 89.5 to 97.7) in the placebo group, and 97.9% (95% CI, 95.6 to 100) in the watch-and-wait cohort. Estimated 10-year survival rates from diagnosis were 86.5% (95% CI, 78.7 to 94.3, placebo), 89.8% (95% CI, 83.3 to 96.3, ibrutinib), and 95.3% (95% CI, 91.1 to 99.4, watch and wait). In the ibrutinib group, one of 12 deaths was CLL-associated, compared with four of 14 fatal cases of CLL progression or Richter transformation in the placebo group. Adverse and serious adverse events occurred in 99.4% and 60% of both treatment groups, respectively. The safety profile indicated increased cardiovascular toxicity in the ibrutinib group.

CONCLUSION
Ibrutinib treatment in early-stage CLL delayed disease progression compared with placebo. However, with the given observation time and few deaths, no survival benefit was demonstrated. In the era of targeted therapies, watch and wait remains the standard of care irrespective of risk factors.
Unveiling Swelling and Erosion Dynamics: Early Development Screening of Mirabegron Extended Release Tablets
Authors: Sousa Ana S. , Serra J. , Estevens C. , Costa R. , Ribeiro António J. 
Published: November 2024

AbstractAlthough the development of extended release (ER) matrices has been extensively investigated, understanding the most appropriate mechanism of drug release to achieve the desired release remains a cost- and time-consuming challenge in the early stages of formulation development. This study aimed to investigate the early stage of developing ER hydrophilic matrix tablets containing mirabegron as a model drug, focusing on the effects of polymer type, diluent type, and polymer amount on critical quality attributes (CQAs), namely, tablet swelling and erosion behavior. A full factorial design was employed to explore the interactions of control factors through multivariate regression analysis, emphasizing the application of quality by design (QbD) principles. The swelling and erosion performances of 72 formulations were evaluated. The swelling data were fitted to the Vergnaud model. Finally, in vitro drug release profiles were investigated for four of the formulations studied. The polymer type, diluent type, and polymer amount had distinct effects on the swelling and erosion behavior of the ER matrix tablets. Compared with those with isomalt (G720) or dextrate (DXT), formulations with polyethylene glycol 8000 (P8000) consistently exhibited greater swelling. Additionally, higher molecular weight was correlated with increased swelling within the same polymer type. Hydroxypropylmethylcellulose (HPMC) and polyethylene oxide (PEO)-based formulations showed higher swelling rates, while polyvinyl alcohol (PVA-80) displayed the highest erosion percentage. The findings highlight the significance of incorporating early-stage screening designs to maximize efficiency and optimize time and resource. This approach enables the development of a comprehensive understanding of drug release mechanisms from ER matrix tablets.
Graphical abstract
User-Friendliness Evaluation of Handling pMDI with Various Add-on Devices in Asthmatic Patients
Authors: Abdelfattah Ahmed M. , Sarhan Rania M. , Madney Yasmin M. , Mady Ahmed F. , Abdelrahim Mohamed E. A. , Harb Hadeer S. 
Published: November 2024

AbstractThe objective of this study was to assess the use of pMDI alone and pMDI with different spacers in asthmatic patients and to identify any associations between errors in handling the device for the first time and the sessions needed to reach the correct handling method, considering patient demographics and clinical characteristics. A total of 150 Asthmatic patients were crossed over to handle pMDI alone and with add-on inhalable devices (Aerochamber plus, Tips Haler, Able, Dispozable and Aer-8) randomly, without receiving verbal or demonstrative instruction (baseline assessment). The assessment of the inhaler technique was performed using checklists that had been set beforehand. Subsequently, the proper utilization of the inhaler was exhibited, and the patient's inhaler usage was reassessed. The demonstration was repeated until an optimal technique was attained. The number of counselling attempts required to achieve successful management, together with patient demographics and clinical factors, were documented. The mean percentage of total errors at baseline shows that pMDI alone is significantly higher than pMDI attached to add-on devices (53.90 ± 9.71, 32.54 ± 13.93, 24.53 ± 14.93, 21.6 ± 14.48, 25.14 ± 10.99, 27.47 ± 10.28) for pMDI alone, Aerochamber plus, Tips Haler, Able, Dispozable and Aer-8 respectively at p < 0.01. Able and Tips Haler spacers are significantly lower than other spacers with pMDI and pMDI alone in terms of total sessions needed to attain the complete optimal handling technique at p < 0.01. Weak and very weak correlations were observed between the percentage of total errors at baseline and the total sessions with education years, Montreal Cognitive Assessment, and age as well as some demographics and clinical variables. Handling pMDI can be challenging however the introduction of spacers simplifies this procedure. Different spacers cannot be treated as a homogeneous group due to variations in handling techniques and ease of use. the Able spacer requires the fewest handling steps of any spacer and has the highest percentage of patients who can use it without assistance.
Graphical Abstract
Effect of Bilateral Subthalamic Nucleus (STN) Deep Brain Stimulation (DBS) on drug reduction for Parkinson’s Disease: A retrospective observational study from Pakistan
Authors: Khan Zubair Mustafa , Ahmad Shahzeb , Qadri Haseeb Mehmood , Khizar Ahtesham , Bashir Asif 
Published: November 2024

Objectives: To determine the effect of Bilateral Subthalamic Nucleus (STN) Deep Brain Stimulation (DBS) on drug reduction for Parkinson’s disease (PD) in a low-middle-income country.
Methods: This retrospective cohort study included 49 patients following interview based questionnaires who underwent bilateral STN DBS at the Department of Neurosurgery, Punjab Institute of Neurosciences, Lahore, Pakistan over five years (July 30, 2018 to June 29, 2023). Patients meeting the inclusion and exclusion criteria (49 patients) were selected and the effect of bilateral STN DBS on drug reduction was evaluated.
Results: Following bilateral STN for Parkinsons Disease Levodopa equivalent daily dose (LEDD) and Unified Parkinson’s Disease Rating Scale (UPDRS)-III results were statistically significant, with a P-value of 0.0001. Effect of DBS on UPDRS-IV was 0.2751, which is statistically insignificant. LEDD reduced by 55.03% (P<0.0001), UPRS-III improved by 80.49% (P<0.0001), and UPDRS-IV improved by 1% (P<0.0001). Time spent with dyskinesia reduced by 17.54% (P<0.0001), whereas time spent off period reduced 22.44% (P<0.0001).
Conclusion: When the disease is in its early stages and has not yet manifested advanced Parkinsons symptoms, bilateral STN DBS is an effective treatment option. It considerably reduces the need for levodopa and significantly improves the motor symptoms of rigidity, tremors, and bradykinesia.
List of abbreviations: STN: Subthalamic nucleus, DBS: Deep brain stimulation, PD: Parkinson’s disease, MSA: Multiple system atrophy, PSP: Progressive supranuclear palsy, CBD: Corticobasal degeneration, UPDRS: Unified Parkinson’s Disease Rating Scale, MMSE: Mini mental state examination, MoCA: Montreal cognitive assessment, LEDD: Levodopa equivalent daily dose, PWP: People with Parkinson’s, SEM: Standard error of mean, CI: Confidence interval, LMICs: Low and Middle Income Countries, LEDD: Levo dopa equivalent daily dose, UPDRS: Unified Parkinson’s Disease Rating Scale.
doi: https://doi.org/10.12669/pjms.40.12(PINS).11111
How to cite this: Khan ZM, Ahmad S, Qadri HM, Khizar A, Bashir A. Effect of Bilateral Subthalamic Nucleus (STN) Deep Brain Stimulation (DBS) on drug reduction for Parkinson’s Disease: A retrospective observational study from Pakistan. Pak J Med Sci. 2024;40(12):S25-S31. doi: https://doi.org/10.12669/pjms.40.12(PINS).11111
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.
Punjab Institute of Neurosciences: Annual Report 2023
Authors: Bashir Asif , Qadri Haseeb Mehmood , Bashir Momin 
Published: November 2024

doi: https://doi.org/10.12669/pjms.40.12(PINS).11420
How to cite this: Bashir A, Qadri HM, Bashir M. Punjab Institute of Neurosciences: Annual Report 2023. Pak J Med Sci. 2024;40(12):S4-S5. doi: https://doi.org/10.12669/pjms.40.12(PINS).11420
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.