bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of SOD1 trimerization is a novel drug target for ALS disease
Authors: Woo Tae-gyun , Han Jin , Kim Yuju , Hwang Young Jun , Lee Mua , Kang So-mi , Park Soyoung , Ji Yeongseon , Chung Yeon-Ho , Baek Songyoung , Shin Eunbyeol , Kim Minju , Jang Hyewon , Shin Yun-Jeong , Kwon Yonghoon , Kim Bae-Hoon , Park Bum-Joon 
Published: December 2024

Abstract

Background Amyotrophic lateral sclerosis (ALS) is progressive neurodegenerative disease that begins with cell death of motor neurons in the spinal cord and leads to death from respiratory distress (breathing failure). Most of patients are sporadic type but several genetic causes have been reported. One well-identified genetic variation is a mutation in the SOD1 gene. Indeed, SOD1 aggregation has been reported in ALS patients, but the mechanism of SOD1 aggregation remains unclear. In previous report, we have shown that inhibiting SOD1 aggregation with a hit compound (PRG-A-01) could reduce SOD1-induced cytotoxicity and extended the lifespan of ALS mouse model (SOD1G93A-Tg). However, the compound was poorly bioavailable and rapidly degraded in vivo, necessitating the development a more effective candidate. To overcome these limitations, we generated different derivatives and finally obtained the most plausible drug candidate, PRG-A-04.
Methods To perform in vitro SOD1 aggregation inhibition efficacy of PRG-A-04, neuronal cell lines were transfected with mutant SOD1 expression vectors and incubated with PRG-A-04. SOD1 aggregation was checked by SOD1 oligomerization assay, immunofluorescence and dot blot assay with the misfolded specific SOD1 antibody. The interaction between GST-conjugated SOD1 recombinant proteins and PRG-A-04 was identified using LC-MS/MS and GST-pull down assay. To check in vivo therapeutic effect of PRG-A-04, mouse performance assessment, histological analysis and microarray were profiled on PRG-A-04 injected ALS mouse model (SOD1G93A-Tg)
Results The optimized drug candidate, PRG-A-04, demonstrated favorable pharmacokinetics including high bioavailability and significant blood-brain barrier penetration. Indeed, the oral administration of PRG-A-04 to ALS mouse model could inhibit the aggregation of SOD1 in its spinal cord, protect the neuron loss, and extend lifespan of ALS model mouse up to 3 weeks. Notably, in in vitro experiment, it was confirmed that PRG-A-04 could selectively bind to a mutant form of SOD1, not wild type, and it efficiently inhibit the aggregation caused by SOD1-G147P (SOD1 trimer stabilizer). This specific binding may inhibit the aggregation process of SOD1, which can be caused by mutant SOD1 or other cellular stress conditions.
Conclusions Our findings underscore the potential of treatments targeting trimeric SOD1 in ALS, positioning PRG-A-04 as a strong drug candidate for both familial and sporadic ALS.
The Association Between Temporomandibular Disorders and Kinematics of The Sacroiliac Joint: A 3D motion Analysis Study
Authors: Parchekouhi Ahmad Bahramian , Karimi Noureddin , barzegar Ali , Rahnama Leila 
Published: December 2024

Abstract

Background: Temporomandibular disorders (TMDs) have been the focus of many studies, but the relationship between TMDs and other body segments, such as the pelvis, is still controversial. This study aimed to investigate the relationship between TMD and kinematics of the sacroiliac joint.
Method: Twenty participants with chronic TMD and 20 healthy individuals were included in this study. The temporomandibular joint range of motion, pain intensity, and TMD severity were documented. The three-dimensional kinematics of the sacroiliac joint were recorded during a trunk flexion task using a motion analysis system and MATLAB software.
Results: The severity of TMD had a significant association with pain intensity in the patient group. At the starting position (before forward flexion of the trunk), we found significant differences in the linear and angular positions of the sacrum relative to the ilium in the sagittal plane and around the frontal axis on both sides between groups.
Conclusion: Our results indicated significant differences in some parameters between the healthy and TMD groups, emphasizing altered sacroiliac joint kinematics associated with TMD. This study contributes to the ongoing discussion about the relationship between TMD and other areas of the body and highlights the importance of further research in this area.
Trial registration: Clinical Trial number is not applicable.
Effect and mechanism of lateralization of cerebellar-cerebellar network abnormalities on language in patients with unilateral temporal lobe epilepsy
Authors: Pang Linlin , Chen Zirong , Fan Binglin , Chen Zexiang , Pang Xiaomin , Zhang Zhao , Zhong Cai , Zheng Jinou 
Published: December 2024

Abstract

Objective
Since epilepsy is associated with different levels of cerebral dysfunction, there may be a recombination of language circuits in the course of epilepsy. The cerebellum is part of the whole brain language network. We explored the differences in speech impairment patterns in patients with TLE and different hemiencephalic attacks from the perspective of the cerebellum.
Methods
Fifty-eight patients with TLE and 30 healthy controls were recruited. including 28 patients with left temporal lobe epilepsy (LTLE) and 30 patients with right temporal lobe epilepsy (RTLE). The resting state functional connection method was used to investigate the effects of lateralization and cerebellar laterality on language function in patients with TLE. The differences in functional connectivity (FC) in the whole cerebellar cortex were compared between the three groups.
Results
The FC analysis of the LTLE, RTLE, and HC groups showed significant differences between the three groups. Compared with the HC group, FC was decreased from the Cerebelum_Crus2_R to the right frontal cortex, from the Cerebelum_7_L to the right frontal cortex in both LTLE and RTLE groups. Compared with the LTLE group, FC was decreased from the Cerebelum_3_R to the left frontal pole, left inferior frontal gyrus, and left frontoorbital cortex in the RTLE group. Compared with the HC group, FC in the RTLE group was decreased between the Cerebelum 9L and right medial superior frontal gyrus and right dorsolateral superior frontal gyrus; between Cerebelum 9R and right medial superior frontal gyrus and left dorsolateral superior frontal gyrus; between Vermis9 and left posterior parietal lobe, between Vermis10 and right angular gyrus; between left middle temporal gyrus and language network; between right middle temporal gyrus and language network.
Conclusion
In the brain regions related to language, patients with RTLE had stronger left hemispheric activation than patients with LTLE. At the node level, the RTLE group had greater language central connection disorder than the HC group. Cerebellar-cerebral FC has different connectivity patterns between LTLE and RTLE groups. Cerebellar injury of TLE may lead to functional reorganization and transfer of language dominance to homologous regions in the other hemisphere.
Effect of thumbtack needle therapy at ST36 on postoperative ileus: A pragmatic randomized controlled trial
Authors: Yin Lanlan , Lu Antian , Yang Wangshuo , Liu Anyi , Zhu Tong , Zhu Li , Lai Senyan , Huang Dongmei , Feng Yongdong 
Published: December 2024

Abstract

Objective
This study aims to evaluate the efficacy of thumbtack needle (TN) therapy at the ST36 acupoint in reducing postoperative ileus (POI) duration following elective abdominal surgery.
Background
Postoperative ileus (POI) is a frequent complication after abdominal surgeries, leading to delayed gastrointestinal recovery. TN therapy, a non-invasive form of acupuncture, has shown promise in promoting gastrointestinal function recovery. However, its specific impact on POI, particularly at the ST36 acupoint, requires further exploration.
Methods
This single-center, single-blind randomized controlled trial enrolled 100 patients undergoing elective abdominal surgery. Patients were randomly assigned to receive either TN therapy at bilateral ST36 acupoints (TN group) or a sham treatment (CON group). The primary outcomes were First Exhaust Time, First Stool Time, and First Eating Time, Gastrointestinal Symptom Rating Scale (GSRS), and inflammatory markers (IL-6 and TNF-α), while secondary outcomes included the Visual Analog Scale (VAS).
Results
Patients in the TN group had significantly shorter First Exhaust Time (23.3 hours vs. 25.9 hours, P = 0.019) and First Stool Time (31.4 hours vs. 34.8 hours, P = 0.011) compared to the CON group. There was no significant difference in First Eating Time (P = 0.652). Additionally, the TN group exhibited lower GSRS scores and reduced levels of IL-6 and TNF-α, indicating a faster recovery and reduced postoperative inflammation.
Conclusion
TN therapy at ST36 acupoint significantly accelerated gastrointestinal recovery and reduced postoperative inflammation in patients with POI, providing a promising non-pharmacological treatment option for enhancing recovery post-surgery.
Trial Registration
Tongji Hospital, Huazhong University of Science and Technology (TJ-IRB202403012), Registration date: March 25, 2024. Chinese Clinical Trial Registry (ChiCTR2400090739), Registration Date: October 12, 2024 (additional registration).
Combined Nomogram for Differentiating Adrenal Pheochromocytoma from Large-Diameter Lipid-poor Adenoma Using Multiphase CT Radiomics and clinico-radiological features
Authors: Shan Zujuan , Zhang Xinzhang , Zhang Yiwen , Wang Shuailong , Yang Junfeng , Wang Junfeng , Li Lin , Shi Xin , Li Zhenhui , Xu Ning , Gong Lelan , Da Youguo , Song Wei , Liu Hao , Zhang Xuyuan , Yang Liuyang , Li Wenliang , Yang Liansheng 
Published: December 2024

Abstract

Background and Objective:
Adrenal incidentalomas (AIs) are predominantly adrenal adenomas (80%), with a smaller proportion (7%) being pheochromocytomas(PHEO). Adenomas are typically non-functional tumors managed through observation or medication, with some cases requiring surgical removal, which is generally safe. In contrast, PHEO secrete catecholamines, causing severe blood pressure fluctuations, making surgical resection the only treatment option. Without adequate preoperative preparation, perioperative mortality risk is significantly high.A specialized adrenal CT scanning protocol is recommended to differentiate between these tumor types. However, distinguishing patients with similar washout characteristics remains challenging, and concerns about efficiency, cost, and risk limit its feasibility. Recently, radiomics has demonstrated efficacy in identifying molecular-level differences in tumor cells, including adrenal tumors. This study develops a combined nomogram model, integrating key clinical-radiological and radiomic features from multiphase CT, to enhance accuracy in distinguishing pheochromocytoma from large-diameter lipid-poor adrenal adenoma (LP-AA).
Methods
A retrospective analysis was conducted on 202 patients with pathologically confirmed adrenal PHEO and large-diameter LP-AA from three tertiary care centers. Key clinico-radiological and radiomics features were selected to construct models: a clinico-radiological model, a radiomics model, and a combined nomogram model for predicting these two tumor types. Model performance and robustness were evaluated using external validation, calibration curve analysis, machine learning techniques, and Delong's test. Additionally, the Hosmer-Lemeshow test, decision curve analysis, and five-fold cross-validation were employed to assess the clinical translational potential of the combined nomogram model.
Results
All models demonstrated high diagnostic performance, with AUC values exceeding 0.8 across all cohorts, confirming their reliability. The combined nomogram model exhibited the highest diagnostic accuracy, with AUC values of 0.994, 0.979, and 0.945 for the training, validation, and external test cohorts, respectively. Notably, the unenhanced combined nomogram model was not significantly inferior to the three-phase combined nomogram model (p > 0.05 in the validation and test cohorts; p = 0.049 in the training cohort).
Conclusions
The combined nomogram model reliably distinguishes between PHEO and LP-AA, shows strong clinical translational potential, and may reduce the need for contrast-enhanced CT scans.
Myocardial contractile reserve impairment in patients with Kawasaki disease during convalescent phase: a study based on two-dimensional speckle-tracking stress echocardiography
Authors: Wang Haiyong , Long Xiaoli , Han Zhiming , Dong Xin , Yan Ruiling 
Published: December 2024

Abstract

Background
Persistent myocardial impairment proved by histopathologic studies universally existed in patients with Kawasaki disease (KD), however, the long-term effects on myocardial contractile reserve in KD patients, especially on patients without coronary artery lesions (CALs), is still unknown. The aim of this study was to investigate myocardial contractile reserve in KD patients during late convalescent stage by speckle-tracking adenosine triphosphate (AT) echocardiography.
Methods
A total of 63 antecedent KD patients at least 4 years after the disease onset and 40 age- and gender-matched normal controls were prospectively enrolled. Based on coronary artery status, patients were further divided into CALs group and non-CALs (NCALs) group. Left ventricular ejection fraction (LVEF), speckle-tracking derived-global longitudinal strain (GLS) and global circumferential strain (GCS) were evaluated at rest and during AT peak stress. Myocardial contractile reserve parameters including ΔLVEF, ΔGLS and ΔGCS were defined as the absolute increases in LVEF, GLS and GCS from rest to peak stress.
Results
KD patients regardless of CALs had lower GLS and GCS than normal controls at resting condition. Significant decreases in ΔGLS and ΔGCS were observed in patients with CALs compared to normal controls under peak stress. While ΔGLS and ΔGCS increased in patients without CALs following stress, improvements were significantly weaker than those in normal controls. However, no significant differences in LVEF at rest and ΔLVEF under peak stress between KD patients irrespective of CALs and normal controls were found. In additional, when comparing with patients with NCALs, patients with CALs had lower GLS and GCS at rest, lower ΔGLS and ΔGCS in response to stress.
Conclusions
Subclinical abnormality of myocardial contractile reserve existed in KD patients during late convalescent phase. Even patients without CALs need an additional surveillance on myocardial contractile reserve in the long-term follow-up. These novel findings by speckle-tracking stress echocardiographic analysis may provide more valuable clinical implications for better understanding and long-term management of such patients.
Anterior versus Posterior Transfer of Latissimus Dorsi and Teres Major Tendon in Irreparable Rotator Cuff Tears: A Retrospective Comparative Study
Authors: Baek Chang Hee , Lim Chaemoon , Kim Jung Gon , Kim Bo Taek , Kim Seung Jin 
Published: December 2024

Abstract

Background: There are various options of tendon transfer according to the different types of irreparable rotator cuff tears (IRCTs). However, there were no clear treatment options for the IRCTs involving the anterior, superior and posterior rotator cuff tears (global IRCTs). Latissimus dorsi and teres major (LDTM) could be transferred anteriorly or posteriorly in global IRCTs. The purpose of this study is to evaluate the efficacy of anterior LDTM (aLDTM) transfer and posterior LDTM (pLDTM) transfer in IRCTs.
Methods: The patients who underwent aLDTM transfer (aLDTM group, n=35) for anterosuperior IRCTs or pLDTM transfer (aLDTM group, n=33) for posterosuperior IRCTs between January 2017 and December 2020 were reviewed retrospectively. Clinical and functional outcomes were evaluated based on pain, patient-reported outcome scores, active range of motion (aROM) and strength of aROM. Radiological outcomes were evaluated using arthritic changesin the glenohumeral joint and transferred tendon integrity. Arthritic changes in the glenohumeral joint were evaluated using the acromiohumeral distance (AHD) and Hamada classification on the true anteroposterior radiograph.
Results: No significant intergroup difference was confirmed in patient demographics except for preoperative fat infiltration grade of subscapularis and infraspinatus. The postoperative Constant score, and University of California and Los Angeles (UCLA) score of aLDTM group were significantly higher than that of pLDTM group (p<0.001 and <0.001, respectively). Moreover, the achievement of minimal clinically important difference (MCID) for American Shoulder and Elbow Surgeons score and UCLA score showed a significant difference between two groups (p=0.021 and 0.042, respectively). The postoperative forward elevation (FE) was significantly higher in aLDTM group (p = 0.046). The postoperative FE strength and abduction strength were significantly higher in aLDTM group (p=0.001 and 0.025, respectively). Moreover, the mean improvement of internal rotation strength in aLDTM group was significantly higher than mean improvement of external rotation strength in pLDTM group (p=0.011). The progression of arthritic change was significantly higher in pLDTM group (p=0.002).
Conclusion: Although the aLDTM transfer and pLDTM transfer are effective and safe tendon transfer for IRCTs, aLDTM transfer is more effective than pLDTM transfer due to its biomechanical advantage and tendon transfer principles.
Level of study: level III
Cross-Cultural Perceptions of Police Interview Techniques: A Comparative Study of Indonesian and Dutch Respondents
Authors: Tekin Serra , Irwanda Diandra Yasmine , Bull Ray 
Published: December 2024

Abstract

Conducting an interview can be especially challenging with suspects from cultures different from the interviewer’s own. Previous studies show that a suspect’s culture and communication style (e.g., collectivism/individualism & high/low-context) may affect their response to the interview techniques used by the interviewer. The current study aimed to explore and compare the perception of common interview techniques between two cultures, Indonesian (high-context culture; n = 155) and Dutch (low-context culture; n = 125). After reading a vignette of a fictional crime, participants estimated the likelihood of the suspect giving information in response to various interview techniques. An exploratory factor analysis revealed a five-factor model of interviewing: Humanity, Dominance/Control, Empathy/Perspective-taking, Rapport and Guilt-focused. Indonesian participants perceived the Dominance/Control category as more likely to elicit information from the suspect than did their Dutch counterparts. Moreover, Empathy/Perspective-taking was perceived to be more effective in eliciting information by the Dutch participants than by the Indonesian participants. An examination of the mean scores revealed that both groups perceived Dominance/Control and Guilt-focused techniques as being somewhat effective. The findings indicate that an interviewee’s culture could well play a role in how they respond to the interviewer’s approach. Therefore, the cultural background of the suspect should be taken into consideration while preparing for the interview and also during the interview. Raising more awareness of the consequences of harsher interviewing techniques may also be beneficial.
Recent Incarceration and Minoritized Racial Status as Barriers to the Effectiveness of Recovery Management Checkups
Authors: Kahn Jeffrey , Hart M. Kate , Watson Dennis P. , Allen Caroline B. , Singh Ryan R. , Grella Christine E. , Dennis Michael L. 
Published: December 2024

Abstract

Background: Recovery management checkups done in primary care settings (RMC-PCs) can be an effective intervention to link individuals with substance use disorders (SUD) to treatment and help them stay engaged with treatment. There is reason to question, however, whether RMC-PCs are as effective for those who have been recently incarcerated or for those holding a minoritized, racial identity.
Methods: We examined data from a randomized controlled trial of RMC-PCs compared to a control condition (N = 266).
Results: Multilevel analyses of 4-wave data (3, 6, 9, and 12 months after baseline) indicated that RMC-PCs were more effective than the control condition, especially early in the 12-month study period. The relative effectiveness of RMC-PCs was stronger, however, for participants with fewer days in jail just prior to baseline as well as for White (versus non-White) participants.
Conclusions: These findings suggest the utility of examining potential mediators of these moderated effects in future research as well as tailoring SUD interventions to better meet the needs of these populations.
Trial Registration: ClinicalTrials.gov (NCT03746756).
Utility of Serial LVOT VTI as a Surrogate for Myocardial Performance During Weaning from Temporary Mechanical Circulatory Support in Cardiogenic Shock: A Retrospective Analysis
Authors: Turk Ahmad Z. , AlHammouri Hashim M. , Odeh Nada , Alzoubi Mohammad , Al-Hadeed Faisal , Gobeil Kyle , Kadado A. John , Grewal Vikram , Hernandez-Montfort Jaime 
Published: December 2024

Abstract

Background
Despite ongoing research, robust evidence-based recommendations for daily echocardiographic evaluation to guide the weaning process in patients supported by temporary mechanical circulatory support devices (tMCS) such the Impella or intra-aortic balloon pumps (IABP), are lacking. We propose that protocolized bedside echocardiographic evaluation using left ventricular outflow tract velocity time integral (LVOT VTI) provides a reliable surrogate for myocardial performance before explant.
Methods
This single-center retrospective observational analysis examined patients admitted for cardiogenic shock (CS) requiring tMCS (Impella CP/5.0 and/or IABP) in the cardiac ICU at Baystate Medical Center between 2014 and 2017. A total of 23 patients contributed to 80 LVOT VTI measures and corresponding cardiac index (CI) values spanning the implant-explant period. We plotted three correlation graphs: the first between raw LVOT VTI and CI; the second between indexed LVOT VTI (iVTI, adjusted for body surface area) and CI; and the third between relative LVOT VTI (rVTI) and relative CI (rCI) compared to their initial post-implant values, providing a more accurate evaluation.
Results
The tests demonstrated a strong positive correlation among the variables, with correlation coefficients of r = 0.61, 0.59, and 0.74 for the graphs representing LVOT VTI/CI, iVTI/CI, and rVTI/rCI, respectively.
Conclusion
Our data supports the routine evaluation of LVOT VTI as a surrogate for myocardial performance in CS cases requiring prolonged mechanical unloading. This approach should be further developed and standardized for daily assessment during weaning in shock centers. Further research is needed to establish specific cut-offs associated with long-term myocardial recovery or remission.