bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intensive cycles of neoadjuvant camrelizumab combined with chemotherapy in locally advanced esophageal squamous cell carcinoma: a single-arm, phase II trial
Authors: Yang Guozhen , Su Xiaodong , Huang Yuanheng , Luo Guangyu , Wang Zhiqiang , Cai Peiqiang , Zheng Yating , Bei Ting , Huang Mengli , Bai Yuezong , He Haoqiang , Xiang Jin , Cai Muyan , Zhong Jiudi , Guo Qiyu , Zhang Xu 
Published: June 2023

Abstract
Background
Two cycles of neoadjuvant PD-1 blockade plus chemotherapy induced favorable pathological response and tolerant toxicity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, approximately 25% of patients relapsed within 1 year after surgery, indicating that a short course of treatment may not be sufficient. Therefore, exploring the effects of intensive treatment is needed for optimal clinical outcomes.

Methods
Locally advanced ESCC patients were administered three cycles of camrelizumab plus nab-paclitaxel and capecitabine, followed by thoracoscopic esophagectomy. The primary endpoint was pathologic response. Secondary endpoints included safety, feasibility, radiologic response, survival outcomes, and immunologic/genomic correlates of efficacy.

Results
Forty-seven patients were enrolled in the study. Forty-two patients received surgery, and R0 resection was achieved in all cases. The complete and major pathological response rates were 33.3% and 64.3%, respectively, and the objective response rate was 80.0%. Three cycles of treatment significantly improved T down-staging compared to two cycles (P = 0.03). The most common treatment-related adverse events were grades 1–2, and no surgical delay was reported. With a median follow-up of 24.3 months, the 1-year disease-free survival and overall survival rates were both 97.6%, and the 2-year disease-free survival and overall survival rates were 92.3% and 97.6%, respectively. Three patients experienced disease recurrence or metastasis ranging from 12.5 to 25.8 months after surgery, and one patient died 6 months after surgery due to cardiovascular disease. Neither programmed death-ligand 1 expression nor tumor mutational burden was associated with pathological response. An increased infiltration of CD56dim natural killer cells in the pretreatment tumor was correlated with better pathological response in the primary tumor.

Conclusions
It seems probable that intensive cycles of neoadjuvant camrelizumab plus nab-paclitaxel and capecitabine increased tumor regression and improved survival outcomes. Randomized controlled trials with larger sample sizes and longer follow-up periods are needed to validate these findings.
Trial registration Chinese Clinical Trial Registry, ChiCTR2000029807, Registered February 14, 2020, https://www.chictr.org.cn/showproj.aspx?proj=49459.
Detection of reed using cnn method and analysis of the dry reed (phragmites australis) for a sustainable lake area
Authors: Obreja Cristian Dragos , Buruiana Daniela Laura , Mereuta Elena , Muresan Alina , Ceoromila Alina Mihaela , Ghisman Viorica , Axente Roxana Elena 
Published: June 2023

Abstract
Background
Common reed (Phragmites australis L.) is a highly productive wetland plant and a possible valuable resource of renewable biomass worldwide. For a sustainable management the exploitation of reed is beneficial because the increasing demand for sustainable biomass which presents reed bed areas and wetlands. Knowing the properties of plant biomass obtained from reeds is essential both for the effect on combustion equipment and for the impact on the environment. Brates Lake, situated in Galati, Romania is a natural watershed with reed plantations.

Results
We used the convolutional neural network method combined with the cropped image techniques represent a powerful tool for high-precision image-based biomass detection in lake areas. The study aimed to investigate the morphological and chemical parameters through SEM–EDX analysis and pH, conductivity, nitrate anion, nitrite anion, total nitrogen, sulphate anion, sulphide anion, phosphate anion concentrations were determined from reed extract. The samples have a moderately acidic reaction pH 4.91–4.98. The number of soluble salts in the reed extract is in the range of 3.24–4.70 g/L, the values are within normal limits, providing the plant with the necessary nutrients.

Conclusions
This is the first time that neural networks are used for the detection and prediction of areas at risk for biodiversity (reduction of water gloss until it disappears, imbalances caused by keeping reeds dry in water) caused by the aggressive and uncontrolled growth of reeds.
Assessing and managing frailty in emergency laparotomy: a WSES position paper
Authors: Tian Brian W. C. A. , Stahel Philip F. , Picetti Edoardo , Campanelli Giampiero , Di Saverio Salomone , Moore Ernest , Bensard Denis , Sakakushev Boris , Galante Joseph , Fraga Gustavo P. , Koike Kaoru , Di Carlo Isidoro , Tebala Giovanni D. , Leppaniemi Ari , Tan Edward , Damaskos Dimitris , De’Angelis Nicola , Hecker Andreas , Pisano Michele , YunfengCui  , Maier Ron V. , De Simone Belinda , Amico Francesco , Ceresoli Marco , Pikoulis Manos , Weber Dieter G. , Biffl Walt , Beka Solomon Gurmu , Abu-Zidan Fikri M. , Valentino Massimo , Coccolini Federico , Kluger Yoram , Sartelli Massimo , Agnoletti Vanni , Chirica Mircea , Bravi Francesca , Sall Ibrahima , Catena Fausto 
Published: June 2023

AbstractMany countries are facing an aging population. As people live longer, surgeons face the prospect of operating on increasingly older patients. Traditional teaching is that with older age, these patients face an increased risk of mortality and morbidity, even to a level deemed too prohibitive for surgery. However, this is not always true. An active 90-year-old patient can be much fitter than an overweight, sedentary 65-year-old patient with comorbidities. Recent literature shows that frailty—an age-related cumulative decline in multiple physiological systems, is therefore a better predictor of mortality and morbidity than chronological age alone. Despite recognition of frailty as an important tool in identifying vulnerable surgical patients, many surgeons still shun objective tools. The aim of this position paper was to perform a review of the existing literature and to provide recommendations on emergency laparotomy and in frail patients. This position paper was reviewed by an international expert panel composed of 37 experts who were asked to critically revise the manuscript and position statements. The position paper was conducted according to the WSES methodology. We shall present the derived statements upon which a consensus was reached, specifying the quality of the supporting evidence and suggesting future research directions.
High return to sport rate and good patient-reported outcomes in recreational athletes following simple elbow dislocations
Authors: Nolte Philip-Christian , Vorm Walde Melina , Elrick Bryant P. , Grützner Paul-Alfred , Porschke Felix , Schnetzke Marc 
Published: June 2023

Abstract
Background
The purpose of this study was to investigate outcomes and return to sport metrics in recreational athletes who suffered simple elbow dislocations and were treated operatively or nonoperatively.

Methods
The study included patients between the ages of 16 and 65 who were recreational athletes and had experienced a simple elbow dislocation, with at least 2 years having passed since the injury. Patient-reported outcomes including Mayo Elbow Performance Score (MEPS), Subjective Elbow Value (SEV), Oxford Elbow Score (OES) and Visual Analog Scale (VAS) were collected. Return to sport metrics were assessed.

Results
A total of 44 patients (21 females, mean age 43.8 years [95% CI, 39.1–48.5]) who were recreational athletes before their injury completed follow-up at mean 7.6 years (95% CI, 6.7–8.5). There were 29 patients (65.9%) who were treated operatively. Mean MEPS was 93.3 (95% CI, 90.2–96.4), mean SEV was 94.9 (95% CI, 91.9–97.9) and mean OES was 43.3 (95% CI, 41.3–45.4). A total of 36 (81.8%) patients returned to their pre-injury sport. Mean time to return to sport was 21.7 (95% CI, 16.8–26.5) weeks. There was a significant difference in OES (P = .019) and SEV (P = .030) that favored the nonoperative group; however, no significant differences for MEPS, VAS, satisfaction, arc of motion and return to sport were present between groups. A total of five (11.4%) complications were observed and one (2.3%) required revision.

Conclusions
Good outcomes and a high return to sport rate can be expected in recreational athletes following operative and nonoperative treatment of simple elbow dislocations. However, as many as one-in-five patients may not return to pre-injury sport.
Long-term clinical benefits of delayed-release cysteamine bitartrate capsules in patients with nephropathic cystinosis (response to “A comparison of immediate release and delayed release cysteamine in 17 patients with nephropathic cystinosis”)
Authors: Langman Craig B. 
Published: June 2023

AbstractThe aim of this letter to the editor is to summarize the results from three clinical trial programs evaluating delayed-release cysteamine bitartrate (DR-CYS), which demonstrated the long-term clinical benefits in patients with nephropathic cystinosis when dosed every 12 h. The authors of “A comparison of immediate release and delayed release cysteamine in 17 patients with nephropathic cystinosis” presented recommendations altering the dosage and dosing scheme from what has been previously approved by the FDA for DR-CYS. In this letter to the editor, we critique the authors’ aforementioned article as it is a retrospective analysis of a small number of patients and does not follow the dosing recommendation by the FDA for equivalent dosing of DR-CYS to immediate-release cysteamine bitartrate (IR-CYS). In addition, the article does not include study data to properly support the authors’ suggestion of increased dosing effects and benefits. We present a summary of the results from the DR-CYS clinical trial program and evidence of the rigor from which the clinical data for DR-CYS were generated and recommendation for usage as prescribed.
Targeted degradation of ⍺-synuclein aggregates in Parkinson’s disease using the AUTOTAC technology
Authors: Lee Jihoon , Sung Ki Woon , Bae Eun-Jin , Yoon Dabin , Kim Dasarang , Lee Jin Saem , Park Da-ha , Park Daniel Youngjae , Mun Su Ran , Kwon Soon Chul , Kim Hye Yeon , Min Joo-Ok , Lee Seung-Jae , Suh Young Ho , Kwon Yong Tae 
Published: June 2023

Abstract
Background
There are currently no disease-modifying therapeutics for Parkinson’s disease (PD). Although extensive efforts were undertaken to develop therapeutic approaches to delay the symptoms of PD, untreated α-synuclein (α-syn) aggregates cause cellular toxicity and stimulate further disease progression. PROTAC (Proteolysis-Targeting Chimera) has drawn attention as a therapeutic modality to target α-syn. However, no PROTACs have yet shown to selectively degrade α-syn aggregates mainly owing to the limited capacity of the proteasome to degrade aggregates, necessitating the development of novel approaches to fundamentally eliminate α-syn aggregates.

Methods
We employed AUTOTAC (Autophagy-Targeting Chimera), a macroautophagy-based targeted protein degradation (TPD) platform developed in our earlier studies. A series of AUTOTAC chemicals was synthesized as chimeras that bind both α-syn aggregates and p62/SQSTM1/Sequestosome-1, an autophagic receptor. The efficacy of Autotacs was evaluated to target α-syn aggregates to phagophores and subsequently lysosomes for hydrolysis via p62-dependent macroautophagy. The target engagement was monitored by oligomerization and localization of p62 and autophagic markers. The therapeutic efficacy to rescue PD symptoms was characterized in cultured cells and mice. The PK/PD (pharmacokinetics/pharmacodynamics) profiles were investigated to develop an oral drug for PD.

Results
ATC161 induced selective degradation of α-syn aggregates at DC50 of ~ 100 nM. No apparent degradation was observed with monomeric α-syn. ATC161 mediated the targeting of α-syn aggregates to p62 by binding the ZZ domain and accelerating p62 self-polymerization. These p62-cargo complexes were delivered to autophagic membranes for lysosomal degradation. In PD cellular models, ATC161 exhibited therapeutic efficacy to reduce cell-to-cell transmission of α-syn and to rescue cells from the damages in DNA and mitochondria. In PD mice established by injecting α-syn preformed fibrils (PFFs) into brain striata via stereotaxic surgery, oral administration of ATC161 at 10 mg/kg induced the degradation of α-syn aggregates and reduced their propagation. ATC161 also mitigated the associated glial inflammatory response and improved muscle strength and locomotive activity.

Conclusion
AUTOTAC provides a platform to develop drugs for PD. ATC161, an oral drug with excellent PK/PD profiles, induces selective degradation of α-syn aggregates in vitro and in vivo. We suggest that ATC161 is a disease-modifying drug that degrades the pathogenic cause of PD.
Dynamics of hospitalizations and staffing of Ukraine’s mental health services during the Russian invasion
Authors: Pinchuk Irina , Goto Ryunosuke , Kolodezhny Oleksiy , Pimenova Nataliia , Skokauskas Norbert 
Published: June 2023

Abstract
Background
Since February 2022, the people of Ukraine have experienced devastating losses due to the Russian invasion, increasing the demand for mental healthcare across the nation. Using longitudinal data on mental health facilities across the nation up to summer 2022, we aimed to provide an updated picture of Ukrainian mental health services during the 2022 Russian invasion.

Methods
We conducted a nationwide longitudinal study on Ukrainian inpatient mental health facilities during the Russian invasion since February 2022. We obtained responses from the heads of 30 inpatient mental health facilities, which represent 49.2% of all psychiatric hospitals in Ukraine. Information on hospitalizations and the number, displacement, and injuries of staff in April and July-September 2022 was obtained from each facility.

Results
Facilities across Ukraine reported similar staff shortages in both April and August-September 2022, despite an increase in the number of hospitalizations in July 2022 and a similar percentage of hospitalizations related to war trauma (11.6% in July vs. 10.2% in April, Wilcoxon signed-rank test P = 0.10). Hospitalizations related to war trauma became more dispersed across the nation in July 2022, likely reflecting the return of internally and externally displaced persons to their original locations.

Conclusions
The mental health needs and services changed drastically in the first half-year of the Russian invasion of Ukraine, with those in need more dispersed across the country over time. International aid may need to be scaled up to stably provide mental healthcare, given the displacement of the mental healthcare workforce.
Randomized controlled trial for selective preventive transdiagnostic intervention for adolescents at risk for emotional disorders
Authors: Vivas-Fernandez Manuel , Garcia-Lopez Luis-Joaquin , Piqueras Jose A. , Muela-Martinez Jose-Antonio , Canals-Sans Josefa , Espinosa-Fernandez Lourdes , Jimenez-Vazquez David , Diaz-Castela Maria del Mar , Morales-Hidalgo Paula , Rivera Maria , Ehrenreich-May Jill 
Published: June 2023

AbstractSignificant evidence does exist on the effectiveness of transdiagnostic interventions to improve emotional problems in clinical populations, and their application as universal and indicated prevention programs. However, no randomized controlled trials (RCT) studying selective transdiagnostic prevention intervention have been published. This is the first known RCT to evaluate the efficacy/effectiveness of an evidence-based selective prevention transdiagnostic program for emotional problems in adolescents. The impact of three different interventions was evaluated: (1) PROCARE (Preventive transdiagnostic intervention for Adolescents at Risk for Emotional disorders), which is a group-based, abbreviated version of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A), along with adding a booster session to reduce risk of onset of anxiety and depression, (2) PROCARE + , which includes the PROCARE protocol along with personalized add-on modules tailored to match adolescents’ risk factors, and (3) an active control condition (ACC) based on emotional psychoeducation. In total, 208 adolescents (48.5% girls) evidencing high risk and low protective factors were randomized and allocated to PROCARE, PROCARE + or ACC. Data from 153 adolescents who completed all assessments in the different phases of the study were analyzed. Self- and parent-reported measures were taken at baseline, as well as after the intervention, a 6 month follow-up was carried out, together with a 1 month follow-up after the booster session. Differences between conditions were significant on most of the outcome measures, with superior effect sizes for PROCARE + in the short and long term. Interventions were acceptable in terms of acceptability, with good satisfaction rates. Tailored targeted selective transdiagnostic interventions focused on mitigating risk factors and promoting protective factors in vulnerable adolescents are promising.
Development and validation of a clinical tool to semi‐automatic measure three‐dimensional TAR alignment on two‐dimensional radiographs
Authors: van Hoogstraten Sanne W. G. , Hermus Joris , Verbiest Vera , van Rietbergen Bert , Arts Jacobus J. C. 
Published: June 2023

AbstractBackgroundMalalignment is often postulated as an important reason for the high failure rate of total ankle replacements (TARs). The correlation between TAR malalignment and clinical outcome, however, is not fully understood. Improving and expanding radiographic TAR alignment measurements in the clinic might lead to a better insight into the correlation between malalignment and the clinical outcome. This study aims to develop and validate a tool to semi‐automatic measure TAR alignment, and to improve alignment measurements on radiographs in the clinic.MethodsA tool to semi‐automatically measure TAR alignment on anteroposterior and lateral radiographs was developed in MATLAB. Using the principle of edge contouring and the perpendicular relationship between the anteroposterior and lateral radiographs, the exact configuration of the TAR components can be found. Two observers validated the tool by measuring TAR alignment of ten patients using the tool. The Intraclass Coefficient (ICC) was calculated to assess the reliability of the developed method. The results obtained by the tool were compared to clinical results during radiographic follow‐up in the past, and the accuracy of both methods was calculated using three‐dimensional CT data.ResultsThe tool showed an accuracy of 76% compared to 71% for the method used during follow‐up. ICC values were 0.94 (p < 0.01) and higher for both inter‐and intra‐observer reliability.ConclusionsThe tool presents a reproducible method to measure TAR alignment parameters. Three‐dimensional alignment parameters are obtained from two‐dimensional radiographs, and as the tool can be applied to most TAR designs, it offers a valuable addition in the clinic and for research purposes.
VarID2 quantifies gene expression noise dynamics and unveils functional heterogeneity of ageing hematopoietic stem cells
Authors: Rosales-Alvarez Reyna Edith , Rettkowski Jasmin , Herman Josip Stefan , Dumbović Gabrijela , Cabezas-Wallscheid Nina , Grün Dominic 
Published: June 2023

AbstractVariability of gene expression due to stochasticity of transcription or variation of extrinsic signals, termed biological noise, is a potential driving force of cellular differentiation. Utilizing single-cell RNA-sequencing, we develop VarID2 for the quantification of biological noise at single-cell resolution. VarID2 reveals enhanced nuclear versus cytoplasmic noise, and distinct regulatory modes stratified by correlation between noise, expression, and chromatin accessibility. Noise levels are minimal in murine hematopoietic stem cells (HSCs) and increase during differentiation and ageing. Differential noise identifies myeloid-biased Dlk1+ long-term HSCs in aged mice with enhanced quiescence and self-renewal capacity. VarID2 reveals noise dynamics invisible to conventional single-cell transcriptome analysis.
Synthesis and tyrosinase inhibitory activities of novel isopropylquinazolinones
Authors: Hashemi Arshia , Noori Milad , Dastyafteh Navid , Sadat-Ebrahimi Seyed Esmaeil , Fazelzadeh Haghighi Negin , Mehrpour Katayoun , Sattarinezhad Elahe , Jalali Zafrei Fatemeh , Irajie Cambyz , Daneshmehr Mohammad Ali , Heydari Majid , Larijani Bagher , Iraji Aida , Mahdavi Mohammad 
Published: June 2023

AbstractTo find new anti-browning and whitening agents in this study, new series of isopropylquinazolinone derivatives were designed and synthesized. All derivatives were evaluated as possible tyrosinase inhibitors and compound 9q bearing 4-fluorobenzyl moieties at the R position exhibited the best potencies with an IC50 value of 34.67 ± 3.68 µM. The kinetic evaluations of 9q as the most potent derivatives recorded mix-type inhibition. Compounds 9o and 9q also exhibited potent antioxidant capacity with IC50 values of 38.81 and 40.73 µM, respectively confirming their antioxidant potential. Molecular docking studies of 9q as the most potent derivative were exacuated and it was shown that quinazolinone and acetamide moieties of compound 9q participated in interaction with critical His residues of the binding site. The obtained results demonstrated that the 9q can be considered a suitable pharmacophore to develop potent tyrosinase inhibitors.
Association study between drug prescriptions and Alzheimer’s disease claims in a commercial insurance database
Authors: Hu Eric , Li Tong Shu , Wineinger Nathan E. , Su Andrew I. 
Published: June 2023

Abstract
In the ongoing effort to discover treatments for Alzheimer’s disease (AD), there has been considerable focus on investigating the use of repurposed drug candidates. Mining of electronic health record data has the potential to identify novel correlated effects between commonly used drugs and AD. In this study, claims from members with commercial health insurance coverage were analyzed to determine the correlation between the use of various drugs on AD incidence and claim frequency. We found that, within the insured population, several medications for psychotic and mental illnesses were associated with higher disease incidence and frequency, while, to a lesser extent, antibiotics and anti-inflammatory drugs were associated with lower AD incidence rates. The observations thus provide a general overview of the prescription and claim relationships between various drug types and Alzheimer’s disease, with insights into which drugs have possible implications on resulting AD diagnosis.