bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timing matters: diurnal spine length variation in pediatric patients during radiotherapy
Authors: Meijer Karin M. , van Dijk Irma W.E.M. , Schonk Tamara J. , Balgobind Brian V. , Loginova Anna , van Wieringen Niek , Bel Arjan 
Published: November 2024

Abstract
Background
During the day-night cycle, gravity and applied stress to the body mass and spine causes a decrease in body height, which is restored overnight. This diurnal spine length variation has not yet been quantified during radiotherapy. Therefore, we aimed to quantify diurnal spine length variation on cone beam CTs (CBCTs) of pediatric patients (< 18 years) who underwent radiotherapy.

Methods
For this retrospective study, we included 32 patients (mean age 10.0, range 2.7–16.1 years) who received image guided radiotherapy between 2012 and 2018 in two institutes. Patients were included when they had two fractions per day, or when fractions were scheduled on varying time slots over the course of treatment. Daily CBCTs were registered to the planning CTs using two automatic registrations relative to the bony anatomy; one to vertebra T11 and one to vertebra L4. For each CBCT, the differences between the cranial-caudal (CC) position of the T11 and L4 vertebrae were calculated. To determine the diurnal spine length variation, the difference in vertebrae position between the morning and afternoon CBCTs was calculated. Furthermore, we investigated the possible correlation of diurnal spine length variation with the time slot differences (time interval) between CBCTs (Spearman’s ρ).

Results
Overall, the median spine length variation was -1.0 (range -3.9–0.1) mm, and we found a significant reduction in spine length over the day (p < 0.001) with substantial variations between patients. Time intervals between CBCTs ranging from 4.0 to 9.5 h were not correlated with spine length reduction (ρ=-0.01; p = 0.95).

Conclusions
We found a small but significant reduction in spine length (vertebrae T11 to L4) over the course of day in pediatric patients undergoing radiotherapy, measured on CBCT imaging. Spine length reduction did not correlate with CBCT time intervals. However, our results indicate that diurnal spine length reduction could induce a setup error during treatment, and therefore should be considered in pediatric radiotherapy.
Potential of natural products and gut microbiome in tumor immunotherapy
Authors: Cao Luchang , Wang Xinmiao , Ma Xinyi , Xu Manman , Li Jie 
Published: November 2024

AbstractImmunotherapy is a novel treatment approach for malignant tumors, which has opened a new journey of anti-tumor therapy. Although some patients will show a positive response to immunotherapy, unfortunately, most patients and cancer types do not achieve an ideal response to immunotherapy. Therefore, it is urgent to search for the pathogenesis of sensitized immunotherapy. This review indicates that Fusobacterium nucleatum, Coprobacillus cateniformis, Akkermansia muciniphila, Bifidobacterium, among others, as well as intestinal microbial metabolites are closely associated with resistance to anti-tumor immunotherapy. While natural products of pectin, inulin, jujube, anthocyanins, ginseng polysaccharides, diosgenin, camu-camu, and Inonotus hispidus (Bull).Fr. P. Karst, Icariside I, Safflower yellow, Ganoderma lucidum, and Ginsenoside Rk3, and other Chinese native medicinal compound prescriptions to boost their efficacy of anti-tumor immunotherapy through the regulation of microbiota and microbiota metabolites. However, current research mainly focuses on intestinal, liver, and lung cancer. In the future, natural products could be a viable option for treating malignant tumors, such as pancreatic, esophageal, and gastric malignancies, via sensitizing immunotherapy. Besides, the application characteristics of different types, sources and efficacy of natural products in different immune resistance scenarios also need to be further clarified through the development of future immunotherapy-related studies.
Dual inhibition of HERs and PD-1 counteract resistance in KRASG12C-mutant head and neck cancer
Authors: Novoplansky Ofra , Jagadeeshan Sankar , Prasad Manu , Yegodayev Ksenia M. , Marripati Divyasree , Shareb Raghda Abu , Greenshpan Yariv , Mathukkada Sooraj , Ben-Lulu Talal , Bhattacharya Baisali , Porgador Angel , Kong Dexin , Brägelmann Johannes , Gutkind J. Silvio , Elkabets Moshe 
Published: November 2024

Abstract
Background
Basket clinical trials targeting the KRASG12C-mutation in solid tumors have shown initial promise, including in orphan KRASG12C head and neck cancer (HNC). However, development of resistance to KRASG12C-mutant-specific inhibitors (KRASG12Ci) remains a major obstacle. Here, we investigated the intrinsic (tumor-cell autonomus) and tumor-microenvironment (TME) mechanisms of resistance to the KRASG12Ci—MRTX849 and AMG510 in a unique syngenic murine KRASG12C-mutated HNC cell line.

Methods
Western-blotting was used for protein abundance and activation, overexpression, and ligand activation studies to verify the intrinsic mechanism of resistance to KRASG12Ci in KRASG12C-mutated HNC cell line, 4NQO-L. In vitro KRASG12C-acquired-resistant cells were developed from 4NQO-L (4NQO-L-AcR). MRTX849/lapatinib combination efficacy, and CD8+ T-cells depletion, were assessed in C57BL/6 J mice and supplementation of anti-PD-1 (αPD-1) to MRTX849/lapatinib was also performed in 4NQO-L– KRASG12Ci-senisitve and 4NQO-L-AcR tumors. Immunohistochemistry (IHC) and Immunoflourescence (IF) analyses were performed to profile the TME and programmed death-ligand 1 (PD-L1) expression in tumors.

Results
Activation and upregulation of EGFR and HER2/3 (pan-HERs) are the intrinsic mechanism of resistance to KRASG12Ci in 4NQO-L cells, and blocking pan-HERs signaling with lapatinib enhanced MRTX849 efficacy in vitro by inhibiting the MAPK and AKT/mTOR pathways. 4NQO-L-AcR upregulated the expression of pan-HERs, and lapatinib treatment re-sensitized 4NQO-L-AcR to MRTX849. In mice, MRTX849 showed a slight anti-tumor effect, but in combination with lapatinib a significant tumor growth delay was observed, but all tumors progressed over time. Histopathology analysis of the TME revealed infiltration of CD8+ T-cells after treatment combination, and these CD8+ T-cells play a key role in MRTX849/lapatinib efficacy. MRTX849/lapatinib treatment upregulated PD-L1 overexpression in both stromal and tumor cells, which presumably suppressed CD8+ T-cells and enabled immune escape and tumor progression. Supplementation of αPD-1 prolonged the progression-free survival of 4NQO-L-bearing mice treated with MRTX849/lapatinib. MRTX849/lapatinib treatment delayed tumor growth of 4NQO-L-AcR in mice; however, the percentages of CD8+ T-cells in 4NQO-L-AcR were low, and supplementation of MRTX849/lapatinib with αPD-1 did not improve the outcome.

Conclusions
Our study highlights the critical need for blocking both intrinsic and extrinsic mechanisms of resistance for the prolonged response and shows that such treatment is ineffective in KRASG12Ci-AcR tumors.
Interventions to modify the habituation of biological responses to repeated stress in healthy adults: a randomized controlled trial
Authors: Janson-Schmitt Johanna , Rohleder Nicolas 
Published: November 2024

Abstract
Background
Changes in response patterns of biological stress systems, including responses of the sympathetic nervous system (SNS) and the hypothalamus–pituitary–adrenal (HPA) axis to repeated stress, can promote the development and progression of chronic diseases via changes in downstream inflammatory processes. The aim of this project is thus to investigate, whether habituation of biological stress system activity including responses of the inflammatory system can be modified. Aiming to test for possible paths of action, a randomized controlled study with two intervention programs designed to manipulate cognitive coping strategies will be carried out. By increasing either ruminative or self-compassionate thoughts among healthy young adults, the intervention programs are expected to affect the regulation of occurring emotions as expressed by the responsiveness of biological systems during repeated stress exposure.

Methods
In this study, a total of 120 healthy adults will complete the Trier Social Stress Test (TSST) on two consecutive days. Immediately after the first stress induction, participants will be randomly assigned to two experimental conditions designed to manipulate cognitive coping strategies (rumination vs. self-compassion) or a control condition. Measures of HPA axis (salivary cortisol) and autonomic activity (salivary alpha amylase, heart rate, heart rate variability) as well as inflammatory markers (plasma interleukin(IL)-6, expression rates of pro- and anti-inflammatory cytokine genes) will be repeatedly assessed throughout the experimental sessions. Response and habituation indices of these measures will be calculated and compared between the experimental conditions and the control condition.

Discussion
The results should provide insight into whether modifying response patterns of biological stress systems could reverse a significant biological mechanism in the development of stress-related diseases.

Trial registration
German Clinical Trials Register (DKRS), DRKS00034790. Registered on August 12, 2024, https://www.drks.de/DRKS00034790.
Barriers and facilitators to medication-assisted treatment for cocaine use disorder among men who have sex with men: a qualitative study
Authors: Hsiang Elaine , Patel Kishan , Wilson Erin C. , Dunham Alexandrea , Ikeda Janet , Matheson Tim , Santos Glenn-Milo 
Published: November 2024

Abstract
Background
Rates of cocaine use disorder (CUD) among men who have sex with men (MSM) are high and rising. Among MSM, cocaine use is associated with negative socioeconomic, medical, and psychological outcomes. There are no FDA-approved pharmacotherapy options to treat CUD, and psychosocial interventions demonstrate limited efficacy. While there have been numerous trials evaluating possible medications for CUD, there is a scarcity of qualitative data on the barriers and facilitators of medication-assisted treatment.

Methods
Semi-structured interviews were conducted with 16 participants enrolled in a phase II randomized control trial evaluating extended-release lorcaserin among MSM with CUD. Participants were asked about their motivations for enrolling in the study, attitudes towards taking a medication for CUD, barriers and facilitators of study pill adherence, and their general study experience. Interviews were analyzed using an inductive and exploratory approach to thematic analysis.

Results
Participants were highly motivated to reduce cocaine use and viewed pharmacotherapy as a viable and desirable treatment option. Pharmacotherapy was seen as having fewer access and adherence structural barriers compared to existing psychosocial therapies. Medication reminders facilitated pill taking, while side effects, travel, and active substance use presented barriers to study pill adherence. Disclosure of study participation within social networks was variable pointing to anticipated substance use and treatment stigma.

Conclusions
Our study highlights important factors affecting the acceptability and uptake of medication-assisted treatment for CUD among a diverse sample of MSM. These findings can help guide the development and implementation of future pharmacotherapy options for CUD and other substance use disorders in this key population.
Cellular senescence in Alzheimer’s disease: from physiology to pathology
Authors: Zhu Jing , Wu Chongyun , Yang Luodan 
Published: November 2024

AbstractAlzheimer’s disease (AD) is one of the most common neurodegenerative disorders, characterized by the accumulation of Aβ and abnormal tau hyperphosphorylation. Despite substantial efforts in development of drugs targeting Aβ and tau pathologies, effective therapeutic strategies for AD remain elusive. Recent attention has been paid to the significant role of cellular senescence in AD progression. Mounting evidence suggests that interventions targeting cellular senescence hold promise in improving cognitive function and ameliorating hallmark pathologies in AD. This narrative review provides a comprehensive summary and discussion of the physiological roles, characteristics, biomarkers, and commonly employed in vivo and in vitro models of cellular senescence, with a particular focus on various cell types in the brain, including astrocytes, microglia, oligodendrocyte precursor cells, neurons, and endothelial cells. The review further delves into factors influencing cellular senescence in AD and emphasizes the significance of targeting cellular senescence as a promising approach for AD treatment, which includes the utilization of senolytics and senomorphics.
The contribution of agricultural inputs in reducing child stunting
Authors: Rogna Marco 
Published: November 2024

AbstractWhile the impact of agricultural inputs on crop yields has received considerable attention, their influence on nutritional outcomes has been somewhat neglected. This study aims to fill this gap by examining the role of agricultural inputs in mitigating child stunting through linear dynamic panel regressions conducted at the country level. By analysing data from approximately half of the world’s countries over a 20-years period, our findings reveal that mineral fertilizers make significant positive contributions to reducing child stunting. Other agricultural inputs, such as per-capita agricultural land and manure exhibit a positive contribution in reducing child stunting, but their statistical significance is obtained only in few models. Surprisingly, irrigation appears to have no impact on alleviating child stunting.
The generation method of orthophoto expansion map of arched dome mural based on three-dimensional fine color model
Authors: Hu Chunmei , Wang Yang , Xia Guofang , Han Yang , Ma Xinjian , Jing Guofeng 
Published: November 2024

Abstract
Murals carry cultural significance and historical information, and are an important channel for understanding ancient social norms, artistic styles, and religious beliefs. At present, the digitization of murals is an important technical means for the protection of cultural heritage. Orthogonal images of murals play a vital role in high-precision recording, preservation, academic research, educational expansion, mural protection, digital exhibition and dissemination. At present, orthogonal images of murals are mostly realized by plane projection, but this method is not suitable for making orthogonal images of arched and dome-shaped murals. To address this problem, this paper proposes a method for generating orthogonal expansion images of arched and dome-shaped murals. This method combines a three-dimensional virtual space simulation model with an RTT virtual camera and adopts a spatial reference orthogonal ray scanning model. First, the detailed three-dimensional color model is fitted to the geometric reference of cylindrical and spherical objects to determine its parameters. Next, for the cylindrical murals on the arch, the orientation of the model is initialized using quaternions, and the viewport matrix is adjusted to obtain the required resolution. Then, the RTT camera is used to perform line orthogonal projection in the viewport, and the fringe projection image is generated by rotating around the cylinder axis according to the inversely calculated rotation angle. For the murals on the dome ceiling, this method is used to segment them according to a certain longitude, and the circumscribed cylinder of the fitted sphere is rotated to perform cylindrical orthogonal line scanning in the segmented area. These individual orthogonal line scan images are carefully spliced together to form a complete orthogonal unfolded image. Finally, a fringe projection image is generated with the central meridian of the unfolded part as the center line, and the fringe projection images are spliced together to obtain the final orthogonal unfolded image. Experiments show that compared with existing methods, this method can generate two-dimensional orthogonal unfolded images with high texture fidelity, minimal texture deformation, and uniform deformation distribution. This study provides a novel perspective on the orthogonal unfolding of quasi-cylindrical and quasi-spherical painted objects, and provides an accurate and diverse data basis for the digitization of murals.
Increased kinematic changes in ascending compared with descending biplanar cut in open wedge high tibial osteotomy—a multibody simulation
Authors: Jörgens Maximilian , Ehreiser Sonja , Schroeder Lennart , Watrinet Julius , Böcker Wolfgang , Holzapfel Boris Michael , Radermacher Klaus , Fürmetz Julian 
Published: November 2024

Abstract
Background
The ascending or descending extended biplanar tibial cut in open wedge high tibial osteotomy (owHTO) not only changes the lower limb anatomy in the coronal plane but also leads to different three-dimensional (3D) changes in the patellofemoral joint. This study aimed to perform a comprehensive analysis of the dynamic biomechanical changes in the knee joint using a multibody simulation model.

Methods
Thirteen 3D computer models derived from lower limb computer tomography scans were used for owHTO. Osteotomies with ascending or descending biplanar cut were simulated for each wedge height from 6 to 12 mm (in 1-mm intervals). Multibody simulation was used to analyze differences in patellar shift, patellar tilt, mediolateral patellar rotation, and tibiofemoral rotation during a squat simulation from 5° to 100° knee flexion.

Results
The main effects of an ascending compared with a descending extended biplanar cut in owHTO were characterized by an increase in lateralization of the patella and rotation, along with reduced tilt. Linear mixed models revealed statistically significant effects of both wedge height and cut variant on knee kinematics at 100° knee flexion, with the influence of the cut variant (ascending/descending) being higher on all analyzed kinematic parameters.

Conclusions
Significant differences in the changes in patellofemoral shift, tilt, rotation, and tibiofemoral rotation were observed when performing owHTO with an ascending versus a descending biplanar cut. Apart from tibiofemoral rotation, the resulting kinematic changes were greater with an ascending cut.
Analysis of Concordance Between Next-Generation Sequencing Assessment of Microsatellite Instability and Immunohistochemistry-Mismatch Repair From Solid Tumors
Authors: Ali-Fehmi Rouba , Krause Harris Benjamin , Morris Robert T. , Wallbillich John J. , Corey Logan , Bandyopadhyay Sudeshna , Kheil Mira , Elbashir Leana , Zaiem Fadi , Quddus M. Ruhul , Abada Evi , Herzog Thomas , Karnezis Anthony N. , Antonarakis Emmanuel S. , Kasi Pashtoon Murtaza , Wei Shuanzeng , Swensen Jeffrey , Elliott Andrew , Xiu Joanne , Hechtman Jaclyn , Spetzler David , Abraham Jim , Radovich Milan , Sledge George , Oberley Matthew J. , Bryant David 
Published: November 2024

PURPOSE
The new CAP guideline published in August 2022 recommends using immunohistochemistry (IHC) to test for mismatch repair defects in gastroesophageal (GE), small bowel (SB), or endometrial carcinoma (EC) cancers over next-generation sequencing assessment of microsatellite instability (NGS-MSI) for immune checkpoint inhibitor (ICI) therapy eligibility and states there is a preference to use IHC over NGS-MSI in colorectal carcinoma (CRC).

METHODS
We assessed the concordance of NGS-MSI and IHC-MMR from a very large cohort across the spectrum of solid tumors.

RESULTS

Of the over 190,000 samples with both NGS-MSI and IHC-MMR about 1,160 were initially flagged as discordant. Of those samples initially flagged as discordant, 50.9% remained discordant after being reviewed by an additional pathologist. This resulted in a final discordance rate of 0.31% (590/191,767). Among CRC, GE, SB and EC, 55.4% of mismatch repair proficient/MSI high (MMRp/MSI-H) tumors had at least one somatic pathogenic mutation in an MMR gene or
POLE
. Mismatch repair deficient/microsatellite stable (MMRd/MSS) tumors had a significantly lower rate of high tumor mutational burden than MMRp/MSI-H tumors. Across all solid tumors, MMRd/MSI-H tumors had significantly longer overall survival (OS; hazard ratio [HR], 1.47,
P
< .001) and post-ICI survival (HR, 1.82,
P
< .001) as compared with MMRp/MSS tumors. The OS for the MMRd/MSS group was slightly worse compared to the MMRp/MSI-H tumors, but this difference was not statistically significant (HR, 0.73,
P
= .058), with a similar pattern when looking at post-ICI survival (HR, 0.43,
P
= .155).

CONCLUSION
This study demonstrates that NGS-MSI is noninferior to IHC-MMR and can identify MSI-H tumors that IHC-MMR is unable to detect and conversely IHC-MMR can identify MMRd tumors that NGS-MSI misses.
Analysis of influencing factors and construction of nomogram prediction model of postoperative kinesiophobia in patients undergoing total knee arthroplasty
Authors: Xie Jian , Cai Haoliang , Chen Wenting , Wu Xiaohui , Chen Xi , Guo Jun 
Published: November 2024

Objective: To explore the influencing factors of kinesiophobia and to establish a nomogram prediction model.
Methods: A retrospective observational study was conducted in 354 patients who underwent TKA in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from December 2019 to December 2022. Sociodemographic characteristics, anesthesia methods, Tampa Scale for Kinesiophobia (TSK), numeric rating scale (NRS), hospital for special surgery (HSS), activities of daily living (ADL), and self-rating anxiety scale (SAS) were reviewed and analyzed. Logistic regression analysis was used to identify the influencing factors of kinesiophobia, and a nomogram model was established based on the identified influencing factors and verified by consistency index (C-index), calibration curve, and receiver operating characteristic (ROC) curve.
Results: Incidence of kinesiophobia in patients who received TEAS combined with western medicine (dexmedetomidine and remifentanil) was significantly lower than that in patients who received western medicine alone. The logistic regression analysis showed that family monthly income level, HSS, ADL, and combined TEAS and western medicine approach were independent protective factors for kinesiophobia (all P<0.05). The degree of pain and anxiety were independent risk factors for kinesiophobia (both P<0.05). A nomogram model was constructed with C-index of 0.721 (0.658, 0.784), and the area under curve (AUC) was 0.748 (95 %CI: 0.685-0.807). The calibration curve also showed good consistency between actual observations and nomogram model predictions.
Conclusions: Family monthly income level, anesthesia methods, NRS, HSS, ADL, and SAS scores are influencing factors of kinesiophobia, and the nomogram model can be useful for predicting postoperative kinesiophobia.
doi: https://doi.org/10.12669/pjms.40.11.10306
How to cite this: Xie J, Cai H, Chen W, Wu X, Chen X, Guo J. Analysis of influencing factors and construction of nomogram prediction model of postoperative kinesiophobia in patients undergoing total knee arthroplasty. Pak J Med Sci. 2024;40(11):2550-2557. doi: https://doi.org/10.12669/pjms.40.11.10306
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.
The paradox of healing
Authors: Khan Sheraz Jamal , Iftikhar Mehwash 
Published: November 2024

doi: https://doi.org/10.12669/pjms.40.11.11015
How to cite this: Khan SJ, Iftikhar M. The paradox of healing. Pak J Med Sci. 2024;40(11):2453-2454. doi: https://doi.org/10.12669/pjms.40.11.11015
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.