bluuebunny/crossref_metadata_2025 huggingface dataset:
Tetralogy of Fallot With Pulmonary Atresia and Major Aortopulmonary Collateral Arteries: Diagnostic Modalities—the Role of Computed Tomography, Cardiac Magnetic Resonance Imaging, and Three-Dimensional Modeling
Authors: Ghosh Reena M. , Thompson Mara
Published: February 2025

Cross-sectional imaging modalities facilitate the noninvasive acquisition of anatomic and hemodynamic data in patients with congenital heart disease. This is critical in patients with tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries (TOF PA MAPCAs), who typically undergo multiple surgeries and interventional catheterizations over the course of their lifetime. Advances in cardiac computed tomography (CT) and cardiac magnetic resonance imaging (CMR) have enabled increased spatial resolution imaging and decreased scan times. High spatial resolution datasets provide a comprehensive evaluation of MAPCA anatomy including aortic origin location, lung lobes supplied, and the presence of stenoses. The physiologic data provided by CMR offers a noninvasive assessment of both anatomy and pulmonary blood flow, which can be utilized in decision-making and patient risk stratification. Furthermore, the three-dimensional (3D) datasets acquired by either imaging modality can be used to derive a 3D representation of patient-specific anatomy, visualized in a variety of formats including on-screen volume rendering, 3D prints, digital 3D models, and virtual reality. This article reviews the utility and added value of cardiac CT, CMR, and 3D modeling in the diagnosis and management of patients with TOF/PA/MAPCAs.
Rituximab for children with EBV-positive Burkitt lymphoma in East Africa
Authors: Mawalla William Frank , Achola Caroline , Nabalende Hadijah , Otim Isaac , Legason Ismail , Ogwang Martin David , Aol Pamella Mwa , Sandi Godlove William , Mwamtemi Hadija , Mahawi Salama Omari , Mkwizu Elifuraha , Lyamuya Philomena G , Kamanga Jacqueline Peter , Schroeder Kristin M.S. , Ntemi Paul Shadrack , Chamba Clara Claudius , Vavoulis Dimitris V. , Morrell Liz , Chirande Lulu Fred , Schuh Anna
Published: February 2025

The addition of rituximab to the chemotherapy backbone was shown to significantly improve outcomes of children with aggressive high-grade lymphomas in high-income countries. However, data on its safety, and efficacy in children with Epstein-Barr-Virus-positive Burkitt lymphoma (EBV-positive BL) are limited. We conducted a prospective non-randomized observational study in East African patients up to the age of 25 years with confirmed BL. Patients received either the INCTR-based Standard Chemotherapy (COM) or Rituximab plus standard chemotherapy (R-COM). The primary endpoint was safety. The secondary outcomes were event-free and overall survival and cost-effectiveness of incorporating rituximab. Primary analyses were conducted in the intention-to-treat population. The median follow-up was 23 months. Safety analyses included 72 patients: 32 in the COM group and 42 in the R-COM group. Grade 3 or higher adverse events occurred in 18% of R-COM patients and 16% of COM patients. With respect to treatment outcomes at 12 months, 5 events were observed in the R-COM group and 14 in the COM group. The 12-month event-free survival was 67% with R-COM and 43% with COM (hazard ratio, 0·49; 95% CI, 0·24-0·98; P=0·045). There were eight deaths in the R-COM group, while in the COM group, 16 patients died (hazard ratio, 0·32; 95% CI, 0·14-0·75, P=0·009). R-COM was particularly effective in advanced-stage disease. The addition of rituximab to the INCTR-based protocol (COM) for EBV-positive BL has been observed to be safe and feasible in experienced centres in East Africa and saves lives.
Effect of Pulsed Laser Welding Process on Microstructure, Crystallization, and Mechanical Properties of Zr57Nb5Cu15.4Ni12.6Al10 Bulk Metallic Glass
Authors: Wang Chengyong , Yan Yufu , Ding Feng , Tang Zimin , Chen Weizhuan , Zhu Xuguang
Published: February 2025

Avoiding crystallization while maintaining the original microstructure and mechanical properties of the material are long-term goals of laser welding of Zr-based bulk metallic glass (BMG). In this paper, the effect of pulsed laser welding parameters on the microstructure, crystallization degree, and mechanical properties of Zr57Nb5Cu15.4Ni12.6Al10 BMG is investigated. Non-crystallized welding forming of a zirconium-based amorphous alloy is achieved by optimizing the process parameters of pulsed laser welding. The crystallization degree of Zr-based BMG is mainly determined by the welding speed and power. The welding depth and crystallization area fraction increase with an increase in the effective peak power density. The optimized welding process can effectively reduce the heat accumulation of the weld, thus avoiding crystallization. The flexural strength of the weld can be maintained at 96.5% of the matrix.
(DA-U)2Net: double attention U2Net for retinal vessel segmentation
Authors: Chu Bing , Zhao Jinsong , Zheng Wenqiang , Xu Zhengyuan
Published: February 2025

Background

Morphological changes in the retina are crucial and serve as valuable references in the clinical diagnosis of ophthalmic and cardiovascular diseases. However, the retinal vascular structure is complex, making manual segmentation time-consuming and labor-intensive.

Methods

This paper proposes a retinal segmentation network that integrates feature channel attention and the Convolutional Block Attention Module (CBAM) attention within the U
2
Net model. First, a feature channel attention module is introduced into the RSU (Residual Spatial Unit) block of U
2
Net, forming an Attention-RSU block, which focuses more on significant areas during feature extraction and suppresses the influence of noise; Second, a Spatial Attention Module (SAM) is introduced into the high-resolution module of Attention-RSU to enrich feature extraction from both spatial and channel dimensions, and a Channel Attention Module (CAM) is integrated into the lowresolution module of Attention-RSU, which uses dual channel attention to reduce detail loss.Finally, dilated convolution is applied during the upscaling and downscaling processes to expand the receptive field in low-resolution states, allowing the model to better integrate contextual information.

Results

The evaluation across multiple clinical datasets demonstrated excellent performance on various metrics, with an accuracy (ACC) of 98.71%.

Conclusion

The proposed Network is general enough and we believe it can be easily extended to other medical image segmentation tasks where large scale variation and complicated features are the main challenges.
Surgical vs. non-surgical management of cervical spine fractures associated with ankylosing spinal disorders: a matched retrospective comparison assessing mortality
Authors: Åkerstedt Josefin , Buwaider Ali , El-Hajj Victor Gabriel , Wänman Johan , Frisk Henrik , Blixt Simon , MacDowall Anna , Edström Erik , Elmi-Terander Adrian , Charalampidis Anastasios
Published: February 2025

Background

Ankylosing spinal disorders (ASD) increase the risk of unstable cervical spine fractures, posing a significant mortality risk. Surgery is recommended for patients with neurological deficits, but the effectiveness of non-surgical treatment in those without deficits remains unclear. This study aimed to compare survival rates between surgical and non-surgical treatments of ASD-related cervical fractures in a matched cohort.

Methods

The study analyzed data from the Swedish Fracture Registry (SFR) on adult patients treated for ASD-related cervical spine fractures between January 2015 and December 2021. Preoperative variables included age, sex, trauma type, neurological function, fracture morphology, and treatment method. Propensity score matching was conducted to compare outcomes between treatment groups, ensuring balanced comparison groups regarding age, sex, type of trauma, time from injury to admission, fracture type, level of injury, and neurological function.

Results

In total, 357 adult patients with ASD-related cervical spine fractures were analyzed. Among them, 186 were treated surgically and 171 non-surgically. Treatment failure and conversion so surgical treatment was seen in 3.4% of the non-surgically treated patients. Most patients were male (80%), with a median age of 75 years. Fractures were mainly caused by low-energy trauma (69%). Most patients (92%) were ambulatory (Frankel grade D or E). In the unmatched analysis, surgically treated patients had significantly lower 1-year mortality rates (13% vs. 22%; p < 0.001), but after matching, there were no longer any difference between the two groups (16% vs. 22%; p = 0.44). These findings were also validated on Kaplan–Meier analysis. Multivariable logistic regression analysis identified high age as the only predictor for 30-day mortality (OR 1.14 [95% CI 1.09—1.22], p < 0.001).

Conclusion

Following propensity score matching, surgical and conservative management result in similar mortality outcomes for neurologically intact patients with ASD fractures. Age, rather than treatment approach, emerged as a stronger predictor of overall mortality. Nonetheless, treatment decisions should also consider other clinical outcomes beyond mortality, emphasizing the need for an individualized approach until more robust evidence is available.
Association of glucagon-like peptide-1 receptor agonists with cardiovascular and kidney outcomes in type 2 diabetic kidney transplant recipients
Authors: Lin Li-Chun , Chen Jui-Yi , Huang Thomas Tao-Min , Wu Vin-Cent
Published: February 2025

Background

Cardiovascular disease is a leading cause of post-transplant mortality in kidney transplant recipients (KTRs), especially those with diabetes. Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular and kidney benefits in the general population with type 2 diabetes mellitus (T2DM), evidence regarding their effects in diabetic KTRs is limited.

Methods

This retrospective cohort study utilized data from the Global Collaborative Network in TriNetX, spanning January 1, 2006, to June 1, 2023. Propensity score matching (PSM) with 1:1 ratio was employed to create balanced cohorts. Adult KTRs with T2DM who received GLP-1 RAs within 3 months post-transplant were compared to a matched cohort of KTRs who did not. The primary outcome was all-cause mortality, with secondary outcomes including major adverse cardiovascular events (MACEs) and major adverse kidney events (MAKEs).

Results

A total of 35,488 adult KTRs with T2DM (mean [SD] age, 57.7 [12.2] years; 57.7% men) were identified and 9.8% patients used GLP-1 RAs among 3 months post-transplant. Following PSM, 3564 GLP-1 RAs users were matched with an equal number of nonusers. After a median follow-up of 2.5 years, GLP-1 RAs users had lower risks of mortality (adjusted hazard ratio (aHR), 0.39; 95% CI 0.31–0.50), MACEs (aHR 0.66; 95% CI 0.56–0.79), and MAKEs (aHR 0.66; 95% CI 0.58–0.75). Adverse effects included higher risks of nausea, vomiting and diarrhea, while risks of suicide, hypoglycemia, retinopathy, and pancreatitis were not increased.

Conclusions

In KTRs with T2DM, GLP-1 RAs use was associated with substantial reductions in all-cause mortality, MAKEs, and MACEs compared to nonuse without increasing complications. However, the underutilization of GLP-1 RAs represents a significant opportunity to improve post-transplant outcomes in this high-risk population.

Graphical abstract
Gait stability in virtual reality: effects of VR display modality in the presence of visual perturbations
Authors: Wilson Elizabeth B. , Bergquist J. Stephen , Wright W. Geoffrey , Jacobs Daniel A.
Published: February 2025

Purpose

Virtual reality (VR) has emerged as a pivotal tool for studying balance and postural control mechanisms, leveraging unpredictable visual disturbances that dynamically challenge visuomotor processing. However, the quantity and quality of information available in the visual field may differ between VR systems, potentially introducing conflict with the intended perturbation inputs. Consequently, the extent to which a VR system used in a visual perturbation paradigm influences its ability to elicit compensatory gait behaviors remains unclear. Here we investigate the impact of (1) VR display modality and (2) the direction of visual perturbations on spatiotemporal gait parameters and measures of stability in VR.

Methods

Participants were tasked with maintaining steady-state walking on a self-paced treadmill while viewing a VR scene presented in either a rear-projection curved screen immersive room (IR) or a head-mounted display (HMD). During trials with augmented visual perturbations, pseudorandom oscillations were combined with forward walking speed either in the anterior-posterior (AP), or medio-lateral (ML) direction. Linear mixed-effects models were used to analyze the impact of VR display type and visual perturbations on spatiotemporal gait parameters, stability measures, and joint kinematics.

Results

For self-paced walking in matched VR optic flow, we found that the HMD increased the variability of several parameters related to walking speed control, but did not significantly impact any gait parameter average values. Superimposing visual perturbations along the ML axis increased gait variability and decreased walking stability in both VR systems, but the perturbations had stronger effects if presented in the HMD.

Conclusion

Together, these findings suggest that portable light-weight HMD systems can provide affordable, reliable tools for studying and training balance control and locomotion.
Clinical symptoms and molecular epidemiologic characteristics of varicella patients among children and adults in Ganzhou, China
Authors: Zeng Ting , Lian Chao-Xian , Zhang Xiao-Yi , Liu Ping-Qing , Ao Jian , Zhou Gang-Feng , Chen Xiao-Dong , Huang Dan-Dan , Hu Dian-Gui , Chen Xin
Published: February 2025

Background

Varicella-zoster virus (VZV) is highly transmissible; however, there are limited studies in China.

Methods

The clinical symptoms, disease progression, and laboratory test results of varicella patients among children and adults diagnosed at Ganzhou Fifth People’s Hospital from August 2021 to December 2022 were analysed retrospectively. Genetic polymorphisms in the open reading frame (ORF) 22 and ORF62 fragments of VZV isolates were analysed using molecular epidemiological methods.

Results

Thirty-nine varicella patients were included in this study, 26 of them were children and 13 of them were adults. The incidence of discomfort and complications was significantly greater in adults than in children (P < 0.05). Four adults developed severe disease, one of whom died, with no cases of severe disease or death among children. The 32 VZV clinical isolates were all Clade 2 wild-type strains. Four variant isolates from children had eight base mutations, five of which were missense; two variant isolates from adults had four base mutations, all of which were missense.

Conclusions

The risk of developing severe disease or even death after VZV infection in adults was greater than that in children. There is an urgent need for more studies focusing on the differences in the pathogenicity of VZV in different age groups.
Mechanisms of astrocyte aging in reactivity and disease
Authors: Gildea Holly K. , Liddelow Shane A.
Published: February 2025

Normal aging alters brain functions and phenotypes. However, it is not well understood how astrocytes are impacted by aging, nor how they contribute to neuronal dysfunction and disease risk as organisms age. Here, we examine the transcriptional, cell biology, and functional differences in astrocytes across normal aging. Astrocytes at baseline are heterogenous, responsive to their environments, and critical regulators of brain microenvironments and neuronal function. With increasing age, astrocytes adopt different immune-related and senescence-associated states, which relate to organelle dysfunction and loss of homeostasis maintenance, both cell autonomously and non-cell autonomously. These perturbed states are increasingly associated with age-related dysfunction and the onset of neurodegeneration, suggesting that astrocyte aging is a compelling target for future manipulation in the prevention of disease.
Genomic signals of ecogeographic adaptation in a wild relative are associated with improved wheat performance under drought stress
Authors: Nyine Moses , Davidson Dwight , Adhikari Elina , Clinesmith Marshall , Wang Huan , Akhunova Alina , Fritz Allan , Akhunov Eduard
Published: February 2025

Background

Prioritizing wild relative diversity for improving crop adaptation to emerging drought-prone environments is challenging. Here, we combine the genome-wide environmental scans (GWES) in wheat diploid ancestor Aegilops tauschii (Ae. tauschii) with allele testing in the genetic backgrounds of adapted cultivars to identify diversity for improving wheat adaptation to water-limiting conditions.

Results

We evaluate the adaptive allele effects in Ae. tauschii-wheat introgression lines phenotyped for multiple traits under irrigated and water-limiting conditions using both unmanned aerial system-based imaging and conventional approaches. The GWES show that climatic gradients alone explain more than half of genomic variation in Ae. tauschii, with many alleles associated with climatic factors in Ae. tauschii being linked with improved performance of introgression lines under water-limiting conditions. We find that the most significant GWES signals associated with temperature annual range in the wild relative are linked with reduced canopy temperature in introgression lines and increased yield.

Conclusions

Our results suggest that introgression of climate-adaptive alleles from Ae. tauschii has the potential to improve wheat performance under water-limiting conditions, and that variants controlling physiological processes responsible for maintaining leaf temperature are likely among the targets of adaptive selection in a wild relative. Adaptive variation uncovered by GWES in wild relatives has the potential to improve climate resilience of crop varieties.
Messenger-based assessment of empathic accuracy in couples’ smartphone communication
Authors: Steinebach Philipp , Stein Miriam , Schnell Knut
Published: February 2025

Background

How accurate are empathic judgments of couples in smartphone messenger communication? Are judgments influenced by the level of experience with messengers and communication frequency?.

Objectives

The current preregistered study introduced a novel ecological assessment method and a privacy by design approach to study couples’ empathic accuracy in a messenger context.

Methods

Data from N = 102 participants (51 couples) was used to investigate how accurate judgments of partners’ affect map their partners’ actual affect.

Results

Our results demonstrate tracking accuracy and assumed similarity bias in reciprocal empathic judgments of affective valence and arousal during social messenger texting. A small moderation effect for experience with text messengers was found, indicating that partners with higher experience have a higher bias of assumed similarity when rating their partner’s valence. A small moderation effect for communication frequency confirms that higher messenger communication frequency is associated with more accurate judgments of arousal.

Conclusion

These results point to the reciprocal action of accuracy and bias in couples’ messenger communication and the distinct influences of experience and usage. The feasibility and further application of the ecological messenger-based assessment of couples’ empathic accuracy in interpersonal research are discussed.
Coseismic slip distribution of the 2024 Noto Peninsula earthquake deduced from dense global navigation satellite system network and interferometric synthetic aperture radar data: effect of assumed dip angle
Authors: Yamada Taisuke , Ohta Yusaku , Nishimura Takuya , Yoshida Keisuke , Hiramatsu Yoshihiro , Kinoshita Yohei
Published: February 2025

The Mw 7.5 Noto Peninsula earthquake, which occurred on January 1, 2024, was considerably hazardous to the peninsula and surrounding regions owing to a strong motion, large-scale crustal deformation, and subsequent tsunami. Significant surface displacement was observed by the dense global navigation satellite system (GNSS) stations, including universities and SoftBank corporation sites, and synthetic aperture radar (SAR). To estimate reliable coseismic slip distribution and its uncertainties for this event, we used the dense GNSS and the line-of-sight displacements from the SAR based on the Bayesian optimization framework. Considering the listric fault structure of this source fault, we validated the fault dip angles using the grid-search approach in the slip estimation. The acquired models indicated reverse fault motion, including a right-lateral slip component, and two slip peaks were estimated in the eastern and western regions of the fault in the central peninsula, independent of the assumed dip angles. These locations correspond to regions of significant uplift and westward displacement. The dip angle assumption affects the horizontal and vertical component of the calculated displacements: a higher dip angle model (≥ 45°) well reproduces vertical components of GNSS and synthetic aperture radar displacements, whereas a lower dip angle model (< 45°) well reproduces horizontal displacements. Overall, a fault dip of 45° is plausible, although it is not consistent with the listric structure suggested by the seismic reflection survey and the aftershock distribution below the central part of the peninsula. To test such a listric fault model, we conducted a coseismic slip estimation assuming a relatively high (60°) and low (25°) dip angles for the shallow and deep sections of the fault, respectively. Even in this case, we acquired a slip model similar to that of a plain fault, which reasonably reproduced each component of the surface displacements as well as the simple plane fault models. These results suggest that listric geometry is also acceptable for the source faults of this event, although the flat geometry similarly explains the observations.

Graphical Abstract
Carbon-based nanomaterials: interactions with cells, brain therapies, and neural sensing
Authors: Gárate-Vélez Lorena , Quintana Mildred
Published: February 2025

Carbon nanomaterials (CNMs) are characterized by their extensive surface area and extraordinary electronic, thermal, and chemical properties, offering an innovative potential for biomedical applications. The physicochemical properties of CNMs can be fine-tuned through chemical functionalization to design the bio-nano interface, allowing for controlled biocompatibility or specific bioactivity. This versatility offers a transformative approach to addressing the inherent limitations of conventional brain therapies, which frequently demonstrate low efficacy and significant adverse effects. This review delves into recent advances in understanding the intricate interactions between carbon nanostructures and cellular systems, highlighting their activity in brain therapy and neuronal sensing. We provide a comprehensive analysis of key nanostructures, including few-layer graphene (FLG), graphene oxide (GO), graphene quantum dots (GQD), single- and multi-walled carbon nanotubes (SWCNT and MWCNT), carbon nanohorns (CNH), carbon nanodiamonds (CNDs), and fullerenes (C60). Their unique atomic configurations and surface modifications are examined, revealing the underlying mechanisms that drive their biomedical applications. This review highlights how a deep understanding of the interactions between CNMs and cells can catalyze innovative neurotherapeutic solutions. By leveraging their unique properties, CNMs address critical challenges such as crossing the blood–brain barrier, improving therapeutic accuracy, and minimizing side effects. These advances have the potential to significantly improve the treatment outcomes of brain disorders, paving the way for a new era of targeted and effective neurological interventions.
Global, regional, and national trends in chronic kidney disease burden (1990–2021): a systematic analysis of the global burden of disease in 2021
Authors: Chen Jiaxi , Deng Miao , Zheng Rubin , Chen Yanjin , Pang Wenyi , Zhang Ziyang , Tan Zhouke , Bai Zhixun
Published: February 2025

Background

Chronic kidney disease (CKD) is a global health challenge with diverse etiologies. However, research on the incidence trends of CKD attributable to specific causes remains limited, and the incidence and mortality rates vary across regions. This study aims to identify the patterns and temporal trends of CKD incidence, providing valuable information for the development of targeted prevention strategies and interventions.

Methods

CKD data from the 2021 Global Burden of Disease Study (1990–2021) were analyzed by sex, region, country, cause, and Socio-demographic Index (SDI). Disease burden was assessed using age-standardized incidence (ASIR), mortality rates (ASMR), and estimated annual percentage changes (EAPC). Decomposition analysis evaluated population aging, growth, and epidemiological impacts. The autoregressive integrated moving average (ARIMA) model was used to predict the burden of CKD from 2021 to 2031, and the age-period-cohort (APC) model was employed to assess the effects of age, time, and cohort. Health inequality was analyzed using Slope Index of Inequality (SII) and Concentration Index (CI).

Results

In 2021, Saudi Arabia had the highest ASIR, while Mauritius had the highest mortality. China and India contributed the most cases and deaths. ARIMA forecasts CKD cases will rise to 22.21 million and deaths to 1.81 million by 2031. Epidemiological changes drove incidence growth in medium SDI regions and mortality in high SDI regions. EAPC correlated with ASIR and ASMR. APC analysis showed incidence peaked between 70–80 years, with earlier cohorts facing higher risks. Unknown causes, type 2 diabetes, and hypertension were the leading CKD etiologies. From 1990–2021, health inequality in CKD incidence and mortality worsened, especially in high SDI regions, where the mortality CI shifted from 0.05 to − 0.09.

Conclusions

This study estimated the temporal trends of CKD incidence and mortality globally, as well as at the national and regional levels, from 1990 to 2021. It was observed that countries with higher socio-demographic index (SDI) exhibited unfavorable trends, suggesting that these countries should develop more targeted and specific strategies to address the growing burden of CKD.
Selpercatinib in
RET
Fusion–Positive Non–Small Cell Lung Cancer: Final Safety and Efficacy, Including Overall Survival, From the LIBRETTO-001 Phase I/II Trial
Authors: Gautschi Oliver , Park Keunchil , Solomon Benjamin J. , Tomasini Pascale , Loong Herbert H. , De Braud Filippo , Goto Koichi , Peterson Patrick , Barker Scott , Liming Katherine , Oxnard Geoffrey R. , Frimodt-Moller Bente , Drilon Alexander
Published: February 2025

LIBRETTO-001 (ClinicalTrials.gov identifier:
NCT03157128
) is a registrational phase I/II, single-arm, open-label trial of selpercatinib in RET-dependent cancers. With 19 months of additional follow-up, we report the final efficacy and safety results of selpercatinib in patients with
RET
fusion–positive non–small cell lung cancer (NSCLC) who had previously received platinum-based chemotherapy (N = 247) or were treatment-naïve (N = 69). The objective response rate (ORR) was 62% for pretreated patients and 83% for treatment-naïve patients. Duration of response (DoR) was 31.6 months for pretreated and 20.3 months for treatment-naïve patients (median follow-up approximately 38 months). Median progression-free survival (PFS) was 26.2 months for pretreated and 22.0 months for treatment-naïve patients (median follow-up approximately 40 months). Median overall survival was 47.6 months in pretreated patients and was not reached in the treatment-naïve group (median follow-up approximately 43 months). At the 3-year landmark estimate, 57% of pretreated and 66% of treatment-naïve patients were alive. Among 26 patients with measurable CNS metastases at baseline, the CNS-ORR was 85% with a CNS-DoR of 9.4 months and CNS-PFS of 11.0 months. The safety profile of selpercatinib was consistent with previous reports. With substantial additional follow-up, selpercatinib continued to show durable responses and intracranial activity, with a manageable safety profile in patients with
RET
fusion–positive NSCLC.
Genomic and Immune Landscape of Non–Small Cell Lung Cancer Brain Metastases
Authors: Liu Manlu , Jagodinsky Justin C. , Callahan S. Carson , Minne Rachel L. , Johnson D. Bryan , Tomlins Scott A. , Iyer Gopal , Baschnagel Andrew M.
Published: February 2025

PURPOSE

Metastatic spread of non–small cell lung cancer (NSCLC) to the brain is a commonly occurring and challenging clinical problem, often resulting in patient mortality. Systemic therapies including immunotherapy have modest efficacy in treating brain metastases. Moreover, the local immune environment of brain metastases remains poorly described. This study aims to understand the genomic and immune landscape of NSCLC brain metastases.

METHODS

A total of 3,060 patients with NSCLC sequenced with the Strata Select assay on the Strata Oncology Platform were analyzed. Genomic alterations, tumor mutation burden (TMB),
PD-L1
expression, and immune gene expression were compared across different tissue sites and histologies and within brain metastases.

RESULTS

A significant increase in TMB was observed in the brain metastasis samples compared with nonbrain metastasis samples. Mutations in
TP53
,
KRAS
, and
CDKNA2A
were more prevalent within the brain metastasis cohort compared with other tissue locations. In addition,
PD-L1
expression was significantly decreased within brain metastasis samples compared with other sites. The overall immune landscape within the brain metastasis samples was largely reduced compared with primary lung samples. However, an immune-enriched brain metastasis cohort was identified with higher expressions of
PD-L1
and other immune-related genes.

CONCLUSION

The overall TMB is increased within brain metastases compared with primary lung and other metastasis sites and is associated with a markedly diminished overall immune landscape. The identification of an immune-enriched brain metastasis subgroup suggests potential heterogeneity within the brain metastasis patient cohort, which might have implications for the development of targeted therapies.
NTRK
Fusion–Positive Thyroid Carcinoma: From Diagnosis to Targeted Therapy
Authors: Marczyk Vicente R. , Fazeli Sasan , Dadu Ramona , Busaidy Naifa L. , Iyer Priyanka , Hu Mimi I. , Sherman Steven I. , Hamidi Sarah , Hosseini Sayed Mohsen , Williams Michelle D. , Ahmed Salmaan , Routbort Mark J. , Luthra Raja , Roy-Chowdhuri Sinchita , San Lucas Francis Anthony , Patel Keyur P. , Hong David S. , Zafereo Mark , Wang Jennifer R. , Maniakas Anastasios , Waguespack Steven G. , Cabanillas Maria E.
Published: February 2025

PURPOSE

Neurotrophic tropomyosin receptor kinase (
NTRK
) fusions may act as an oncogenic driver in thyroid carcinomas. Given their low frequency, clinical, pathological, and molecular data on these patients and their responses to targeted therapies are limited.

METHODS

This is an observational retrospective study conducted at a single high-volume cancer center in the United States. Data were retrospectively collected from medical records.

RESULTS

We included 65 patients (37 adult, 28 pediatric) with an
NTRK
fusion–positive thyroid carcinoma (24
NTRK1
, 41
NTRK3
), of which 54 were papillary thyroid carcinomas (PTC), four poorly differentiated thyroid carcinomas (PDTC), and seven anaplastic thyroid carcinomas (ATC). In PTC, an extensive follicular growth pattern was seen in 22 (41%) patients. In adults,
NTRK3
fusions were 3 times more frequent (nine
NTRK1
, 28
NTRK3
), whereas in pediatric patients their frequencies were similar (15
NTRK1
, 13
NTRK3
;
P
= .021). In patients with PDTC/ATC treated with larotrectinib, we detected four emergent solvent front mutations (three
NTRK3
G623R, one
NTRK1
G595R) causing resistance to drug and disease progression. Three of them (two ATC, one PDTC) received second-line selitrectinib on a clinical trial. Partial responses were seen in all three patients, but both patients with ATC progressed within a year.

CONCLUSION

NTRK1
/
3
fusions are seen in PTC, PDTC, and ATC, and a follicular growth pattern was observed in a high proportion of cases. In patients treated with larotrectinib,
NTRK
solvent front mutations are the main resistance mechanism, frequently occurring in PDTC/ATC. Responses to single-agent TRK inhibitor are short-lived in patients with ATC; thus, these drugs should be used with caution in this population.
Gone Gone
Authors: Meyers Todd
Published: February 2025

In Gone Gone, Todd Meyers reckons with grief in the face of overdose death and with the afterlives of loss created by the opioid crisis. Through conversations with friends, lovers, and family members of those who are gone, Meyers brings readers into an inquiry about lives shared, told through tenderness and tragedy. Meyers seeks to find methods to record and convey the many experiences of grief in ways that do not simply consign sorrow to the world of drugs and addiction. Blending prose, poetry, and ethnography, Gone Gone is a lucid and devastating record that reminds readers that the grief felt by those who lose ones they love to overdose is varied and untamable.
The PUF RNA-binding protein, FBF-2, maintains stem cells without binding to RNA
Authors: Carrick Brian H. , Crittenden Sarah L. , Linsley MaryGrace , Costa Dos Santos Stephany J. , Wickens Marvin , Kimble Judith
Published: February 2025

Like all canonical PUF proteins,C. elegansFBF-2 binds to specific RNAs via tripartite recognition motifs (TRMs). Here we report that an FBF-2 mutant protein that cannot bind to RNA, is nonetheless biologically active and maintains stem cells. This unexpected result challenges the conventional wisdom that RBPs must bind to RNAs to achieve biological activity. Also unexpectedly, FBF-2 interactions with partner proteins can compensate for loss of RNA-binding. FBF-2 only loses biological activity when its RNA-binding and partner interactions are both defective. These findings highlight the complementary contributions of RNA-binding and protein partner interactions to activity of an RNA-binding protein.
Anxiety status in outpatients of Type-2 diabetes mellitus
Authors: Khan Azmat Ali , Kanwal Shaista , Khan Jamal Ahmad , Aamir Azizul Hasan
Published: February 2025

Objectives: This study intended to determine the frequency of anxiety in outpatients of Type-2 diabetes mellitus (T2DM) and to evaluate its associated characteristics.
Methods: This cross-sectional observational study was accomplished from July 1, 2023, to December 31, 2023, at the Department of Endocrinology at Hayatabad Medical Complex, Peshawar. The study comprised of individuals with T2DM who were at least 18 years of age and of either gender and who presented to the outpatient department for various reasons. The Beck Anxiety Inventory (BAI) was utilized to assess the respondents’ level of anxiety.
Results: A total of 306 patients with T2DM were enrolled, of whom, 116 (37.9%) were males and 190 (62.1%) were females. The mean age and HbA1c of the participants were 50.7 ± 11.2 years and 12.02 ± 2.03%. Majority (40.2%) of the participants had moderate anxiety while low anxiety and severe level of anxiety were reported by 30.4% and 29.4% participants, respectively. There was a statistically significant association of anxiety with gender, education, employment, family history, comorbidities, and HbA1c. Educated patients (OR=2.7, 95% CI 1.5 to 5.01 p=0.001), and those with comorbidities (OR= 2.3, 95% CI 0.91 to 5.98, p=0.01) had higher odds for occurrence of anxiety.
Conclusion: Almost 70% of the outpatients of T2DM had moderate to severe anxiety, with most of the clinicodemographic characteristics as potential associated factors. It is crucial for informing clinical practice, enhancing patient care, and promoting better mental health outcomes in this population.
doi: https://doi.org/10.12669/pjms.41.3.10487
How to cite this: Khan AA, Kanwal S, Khan JA, Aamir AH. Anxiety status in outpatients of Type-2 diabetes mellitus. Pak J Med Sci. 2025;41(3):774-779. doi: https://doi.org/10.12669/pjms.41.3.10487
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.
Effective use of Item Analysis to improve the Reliability and Validity of Undergraduate Medical Examinations: Evaluating the same exam over many years: A different approach
Authors: Zubairi Nadeem Alam , AlAhmadi Turki Saad , Ibrahim Mohamed Hesham , Hegazi Moustafa Abdelaal , Gadi Fahad Ussif
Published: February 2025

Objective: MCQ exams are part of end-module assessments in undergraduate medical institutions. Item Analysis (IA) is the best tool to check their reliability and validity. It provides the Reliability Coefficient KR20, Difficulty Index (DI), Discrimination Index (DISC), and Distractor Efficiency (DE). Almost all research papers on IA are based on single exam analysis. We examined the IA of multiple exams of the same module, taken in four years. We aimed to explore the required consistency over the years and the effectiveness of IA-based post-exam measures.
Methodology: Item Analysis of eight final MCQ exams of the Pediatric module from 2020-21 to 2023-24, at the Faculty of Medicine in Rabigh, King Abdulaziz University, Saudi Arabia, were included in the study.
Results: All exams had KR20 of 90 and above indicating excellent reliability. Difficulty levels were consistent except for a single year. Discriminative ability was maintained over the years. Only 28 out of 800 MCQs had a negative DISC. All exams maintained good DE. Only 15 MCQs over four years had zero DE. The practice of reviewing all Non-Functional Distractors yielded a gradual improvement in exam quality
Conclusion: Besides the IA of individual exams, it is also recommended that IA of the same exam be evaluated over 4-5 years to see consistency and trends towards improvement. It helps in improving the reliability and validity by addressing deficiencies and deviations from the recommended standards
doi: https://doi.org/10.12669/pjms.41.3.10693
How to cite this: Zubairi NA, AlAhmadi TS, Ibrahim MH, Hegazi MA, Gadi FU. Effective use of Item Analysis to improve the Reliability and Validity of Undergraduate Medical Examinations: Evaluating the same exam over many years: A different approach. Pak J Med Sci. 2025;41(3):810-815.  doi: https://doi.org/10.12669/pjms.41.3.10693
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.
Role of ERG3 mutation and expression in azole resistant Candida albicans isolated from vulvovaginal candidiasis patients
Authors: Zaman Ronaq , Ullah Ihsan , Arif Ambreen
Published: February 2025

Objective: The study aimed to investigate mutations and mRNA expression of the ERG3 gene in resistant Candida albicans isolates.
Methods: This cross-sectional study was conducted from October 2018 to June 2019. High vaginal swab samples were collected from Hayatabad Medical Complex and transported to Khyber Medical University. Samples were inoculated on different media and identified by 20C AUX strips. Antifungal susceptibility was determined using the disc diffusion and broth microdilution methods. The ERG3 gene was amplified and sequenced to find amino acid polymorphisms. Real-time PCR was performed to study level of ERG3 expression.
Results: A total of seventy-three (n=73) Candida albicans out of 369 samples were isolated. Among the isolates 49.3%, 54.8%, 53.4%, 47.9%, 30.1% were resistant to fluconazole, Clotrimazole, Miconazole, Voriconazole and Itraconazole, respectively. Sanger sequencing of ERG3 gene of isolates revealed six synonymous mutations. Expression level of mRNA of ERG3 gene in azoles sensitive stains (3.72±2.22 was higher than those in the resistant Candida albican strains (1.74±0.96).
Conclusion: This study revealed synonymous mutations and low expression of ERG3 gene in azole-resistant C. albican.
doi: https://doi.org/10.12669/pjms.41.3.9325
How to cite this: Zaman R, Ihsan Ullah, Arif A. Role of ERG3 mutation and expression in azole resistant Candida albicans isolated from vulvovaginal candidiasis patients. Pak J Med Sci. 2025;41(3):861-866. doi: https://doi.org/10.12669/pjms.41.3.9325
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.
Aberrant immunophenotypic expressions in childhood acute leukemias: A tertiary care hospital experience
Authors: Saqlain Nazish , Hareem Sidra , Batool Fatima , Mahmood Khalid
Published: February 2025

Background & Objective: Pediatric acute leukemias can present with aberrant immunophenotypes characterized by a different pattern of antigen expression on malignant cells, unlike the process of usual hematopoietic maturation. The objective of this study was to determine the aberrant immunophenotype expressions in newly diagnosed pediatric acute lymphoblastic and acute myeloid leukemias.
Methods: This cross-sectional study was carried out at University of Child Health Sciences, The Children’s Hospital, Lahore, from October 2022 to December 2022 after IRB approval. After taking informed consent from parents/guardians, 290 children diagnosed with acute leukemia were included in the study. Peripheral blood or bone marrow samples in EDTA vial were used for flowcytometric analysis by using BD FACS Canto II flow-cytometer. The data was collected on a pre-designed proforma and analyzed by using IBM-SPSS V-23.
Result: Among 290 cases, Acute Lymphoblastic Leukemia (ALL) constituted 221(76.2%) cases and 69(23.7%) were Acute Myeloid Leukemia (AML). Out of the total, the aberrant antigens were present in 32(11%) patients with 40 total events (18.1% immunophenotype aberrancy rate). The most common aberrant antigens were reported in B-ALL and the most common aberrant expression was of CD13 (62.5%). In AML, the most common aberrant antigen seen was CD19 (55.6%) and in T-ALL the most common were CD117 and HLA-DR (26.6%).
Conclusion: The most aberrant immunophenotypic markers were seen mostly in B-ALL pediatric cases followed by AML and T-ALL. Such abnormal expressions should be kept in mind while diagnosing the children with acute leukemia as they may affect the prognosis.
doi: https://doi.org/10.12669/pjms.41.3.9717
How to cite this: Saqlain N, Hareem S, Batool F, Mahmood K. Aberrant immunophenotypic expressions in childhood acute leukemias: A tertiary care hospital experience. Pak J Med Sci. 2025;41(3):816-820. doi: https://doi.org/10.12669/pjms.41.3.9717
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.
Application of antibiotic-loaded bone cement in treating lower limb soft tissue infection
Authors: Lang Zhigang , Zhang Xu , Liang Yuxiang
Published: February 2025

Objective: To explore the clinical efficacy of antibiotic-loaded bone cement in the treatment of lower limb soft tissue infection.
Methods: A retrospective analysis was carried out on 40 patients with lower limb soft tissue infection who were admitted to Sichuan Orthopedic Hospital from January 1, 2022 to December 1, 2023. The enrolled patients were divided into two groups according to different therapies, including the bone cement treatment (the study group) group and the conventional treatment group (the control group), with 20 cases in each group. Further comparison was made on the number of operations, wound healing time, Grade-A wound healing rate, recurrence rate, and recovery rate of inflammatory indicators between the two groups.
Results: Patients in both groups were followed up, and there was no statistically significant difference in the number of operations between the two groups (P>0.05). The study group had shorter wound healing time (P<0.05), higher Grade-A wound healing rate (P<0.05), lower recurrence rate (P<0.05), and higher normal rate of inflammatory indicators (P<0.05) than those in the control group.
Conclusion: Antibiotic-loaded bone cement showed a clear effect on treating lower limb soft tissue infection, with good wound healing and low recurrence rate.
doi: https://doi.org/10.12669/pjms.41.3.9872
How to cite this: Lang Z, Zhang X, Liang Y. Application of antibiotic-loaded bone cement in treating lower limb soft tissue infection. Pak J Med Sci. 2025;41(3):792-797. doi: https://doi.org/10.12669/pjms.41.3.9872
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 association between Type-D personality and in vitro fertilization success among women with unexplained infertility
Authors: Tola Esra Nur , Kılınçdemir Turgut Ümran
Published: February 2025

Objective: To evalute the association between Type-D personality and in vitro fertilization (IVF) success in unexplained infertile women.
Methods: This was a cross-sectional study conducted at the IVF unit of a tertiary center between September 2017 - December 2019. The 21 items Beck Depression Inventory (BDI-21) and 14 items Type-D Scale (DS14) were noted from 256 unexplained infertile women undergoing an IVF cycle.
Results: Paternal educational level and clinical pregnancy were lower and depression was more prevalent in Type-Ds than non-Type-Ds. There was a positive correlation between BDI-21 scores and duration of infertility and cycle count. Age, paternal educational level, anti-mullerian hormone and metaphaseII number were lower and Type-D personality was more prevalent in women who failed to become pregnant than women who achieved pregnancy. After adjustment of factors affect the IVF success, clinical pregnancy was negatively associated with Type-D personality, age and low paternal educational level, whereas it was positively associated with infertility duration and single embryo transfer.
Conclusion: It seems that having a Type-D personality may negatively affect clinical pregnancy after IVF treatment in couples with unexplained infertility.
doi: https://doi.org/10.12669/pjms.41.3.9966
How to cite this: Tola EN, Turgut UK. The association between Type-D personality and in vitro fertilization success among women with unexplained infertility. Pak J Med Sci. 2025;41(3):730-735. doi: https://doi.org/10.12669/pjms.41.3.9966
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.