bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of ALL With ALL-BFM-95 Protocol in Nepal
Authors: Sharma Poudyal Bishesh , Paudel Bishal , Tuladhar Sampurna , Neupane Samir , Bhattarai Kushal , Joshi Utsav 
Published: July 2023

PURPOSE Data on survival outcomes in patients with acute lymphoblastic leukemia (ALL) originating from Nepal are limited. We aim to present the real-world data on treatment outcomes of patients with de novo ALL treated with pediatric ALL-Berlin-Frankfurt-Muenster (BFM)-95 protocol in Nepal. PATIENTS AND METHODS We used the medical records of 103 consecutive patients with ALL treated in our center from 2013 to 2016 to evaluate the overall survival (OS) and relapse-free survival (RFS) and analyzed the effects of clinicopathologic factors on survival outcomes in patients with ALL. RESULTS The 3-year OS and RFS in the entire cohort was 89.4% (95% CI, 82.1 to 96.7) and 87.3% (95% CI, 79.8 to 94.7), with a mean OS and RFS of 79.4 months (95% CI, 74.2 to 84.5) and 76.6 months (95% CI, 70.8 to 82.4), respectively. Patients with prednisone good response (PGR) showed better mean OS and RFS, whereas complete marrow response on day 33 was associated with better mean OS alone. Patients with Philadelphia (Ph)-positive ALL showed worse mean RFS compared to those with Ph-negative status. On multivariate analysis, PGR (hazard ratio [HR], 0.11; 95% CI, 0.03 to 0.49; P = .004) and sagittal vein thrombosis (SVT; HR, 5.95; 95% CI, 1.30 to 27.18; P = .02) were the only independent predictors of OS and RFS, respectively. Adverse events on BFM-95 protocol included SVT (4.9%), peripheral neuropathy (7.8%), myopathy (20.4%), hyperglycemia (24.3%), intestinal obstruction (7.8%), avascular necrosis of femur (6.8%), and mucositis (46%). CONCLUSION BFM-95 protocol appears to be a safe and effective strategy in adolescent and young adults and adult Nepalese population with ALL with a low toxicity profile.
An AI Approach to Generating MIDD Assets Across the Drug Development Continuum
Authors: Barrett Jeffrey S , Goyal Rahul K , Gobburu Jogarao , Baran Szczepan , Varshney Jyotika 
Published: July 2023

AbstractModel-informed drug development involves developing and applying exposure-based, biological, and statistical models derived from preclinical and clinical data sources to inform drug development and decision-making. Discrete models are generated from individual experiments resulting in a single model expression that is utilized to inform a single stage-gate decision. Other model types provide a more holistic view of disease biology and potentially disease progression depending on the appropriateness of the underlying data sources for that purpose. Despite this awareness, most data integration and model development approaches are still reliant on internal (within company) data stores and traditional structural model types. An AI/ML-based MIDD approach relies on more diverse data and is informed by past successes and failures including data outside a host company (external data sources) that may enhance predictive value and enhance data generated by the sponsor to reflect more informed and timely experimentation. The AI/ML methodology also provides a complementary approach to more traditional modeling efforts that support MIDD and thus yields greater fidelity in decision-making. Early pilot studies support this assessment but will require broader adoption and regulatory support for more evidence and refinement of this paradigm. An AI/ML-based approach to MIDD has the potential to transform regulatory science and the current drug development paradigm, optimize information value, and increase candidate and eventually product confidence with respect to safety and efficacy. We highlight early experiences with this approach using the AI compute platforms as representative examples of how MIDD can be facilitated with an AI/ML approach.
Graphical abstract
Tissue Acceleration as a Novel Metric for Surgical Performance During Carotid Endarterectomy
Authors: Sugiyama Taku , Ito Masaki , Sugimori Hiroyuki , Tang Minghui , Nakamura Toshitaka , Ogasawara Katsuhiko , Matsuzawa Hitoshi , Nakayama Naoki , Lama Sanju , Sutherland Garnette R. , Fujimura Miki 
Published: July 2023

BACKGROUND AND OBJECTIVES:
Gentle tissue handling to avoid excessive motion of affected fragile vessels during surgical dissection is essential for both surgeon proficiency and patient safety during carotid endarterectomy (CEA). However, a void remains in the quantification of these aspects during surgery. The video-based measurement of tissue acceleration is presented as a novel metric for the objective assessment of surgical performance. This study aimed to evaluate whether such metrics correlate with both surgeons' skill proficiency and adverse events during CEA.

METHODS:
In a retrospective study including 117 patients who underwent CEA, acceleration of the carotid artery was measured during exposure through a video-based analysis. Tissue acceleration values and threshold violation error frequencies were analyzed and compared among the surgeon groups with different surgical experience (3 groups: novice, intermediate, and expert). Multiple patient-related variables, surgeon groups, and video-based surgical performance parameters were compared between the patients with and without adverse events during CEA.

RESULTS:
Eleven patients (9.4%) experienced adverse events after CEA, and the rate of adverse events significantly correlated with the surgeon group. The mean maximum tissue acceleration and number of errors during surgical tasks significantly decreased from novice, to intermediate, to expert surgeons, and stepwise discriminant analysis showed that the combined use of surgical performance factors could accurately discriminate between surgeon groups. The multivariate logistic regression analysis revealed that the number of errors and vulnerable carotid plaques were associated with adverse events.

CONCLUSION:
Tissue acceleration profiles can be a novel metric for the objective assessment of surgical performance and the prediction of adverse events during surgery. Thus, this concept can be introduced into futuristic computer-aided surgeries for both surgical education and patient safety.
Simulation study of comparative dosimetric analysis of coplanar horizontal-port scanned carbon-ion beam therapy in the head and neck
Authors: Ebner Daniel , Koto Masashi , Furuichi Wataru , Mori Shinichiro 
Published: July 2023

Objective:
Carbon-ion radiotherapy (CIRT) has demonstrated success in treating radioresistant disease within the head and neck, owing to its unique physical and radiobiological properties. Construction cost remains prohibitive; a center offering only a horizontal port may bridge this difficulty, but removal of the vertical port may prohibit treatment of disease near critical organs-at-risk. Building a center only containing a horizontal treatment port has been proposed as one method for cost savings.

Methods:
20 complex cases of head and neck cancer previously treated with conventional CIRT were retrospectively planned using horizontal-port-only treatment incorporating non-coplanar treatment angles to achieve greater degrees of freedom. These were dosimetrically compared with the previous plans.

Results:
Comparable D95 coverage of both planning target volume and gross tumor volume with ability to meet organ-at-risk constraints were feasible with horizontal-port-only treatment. Collectively differences were noted in PTV D95, brain stem Dmax, contralateral eye Dmax and V10 Gy (RBE); further qualitative differences were noted on a plan-by-plan basis dependent on disease location.

Conclusion:
Horizontal-port-only treatment employing non-coplanar angles was feasible for complicated head and neck disease typically treated with CIRT, though careful consideration is necessary on a plan-by-plan basis.

Advances in knowledge:
It is worth noting that non-coplanar approaches are not typically used with the current treatment gantry and may extend further the difference between horizontal port planning and a gantry-based gold-standard.
The use of Stimulan in bone and joint infections
Authors: Mereddy Praveen , Nallamilli Somasekhar R. , Gowda Veda P. , Kasha Srinivas , Godey Shashi K. , Nallamilli Rajyalakshmi R. , GPRK Rohit , Meda Venu G. R. 
Published: July 2023

AimsMusculoskeletal infection is a devastating complication in both trauma and elective orthopaedic surgeries that can result in significant morbidity. Aim of this study was to assess the effectiveness and complications of local antibiotic impregnated dissolvable synthetic calcium sulphate beads (Stimulan Rapid Cure) in the hands of different surgeons from multiple centres in surgically managed bone and joint infections.MethodsBetween January 2019 and December 2022, 106 patients with bone and joint infections were treated by five surgeons in five hospitals. Surgical debridement and calcium sulphate bead insertion was performed for local elution of antibiotics in high concentration. In all, 100 patients were available for follow-up at regular intervals. Choice of antibiotic was tailor made for each patient in consultation with microbiologist based on the organism grown on culture and the sensitivity. In majority of our cases, we used a combination of vancomycin and culture sensitive heat stable antibiotic after a thorough debridement of the site. Primary wound closure was achieved in 99 patients and a split skin graft closure was done in one patient. Mean follow-up was 20 months (12 to 30).ResultsOverall, six out of 106 patients (5.6%) presented with sepsis and poorly controlled comorbid conditions, and died in the hospital within few days of index surgery. Out of the remaining 100 patients, control of infection was achieved in 95 patients (95%). Persistence of infection was noted in five (5%) patients. Out of these 95 patients that had good control of infection, four patients (4.2%) with gap nonunion needed Masquelet procedure to achieve union.ConclusionOur multicentre experience confirmed that surgical debridement along with calcium sulphate bead insertion was effective in treating bone and joint infections without any side effects and complications.Cite this article: Bone Jt Open 2023;4(7):516–522.
Seroprevalence of Toxoplasma gondii infection among patients of a tertiary hospital in Guangzhou, Guangdong province, PR China
Authors: Guan Yu-bin , Sun Xiao-xiao , Chen Shao-lian , Zhu Xiao-ting , Zeng Zhi-hua , Lu Han-wei , Feng Hong-mei , Guo Yu , Jiang Wen-gong , Xiong Kui , Yang Xiao-rong , Nam Ho-Woo , Yang Zhao-shou 
Published: July 2023

PurposeThis study aimed to explore the prevalence ofToxoplasma gondii(T.gondii) among patients in Guangzhou city, South China, and to identify susceptible patient populations and analyze the causes of infection differences.MethodsFrom May 2020 to May 2022, a total of 637 sera were collected from patients, and 205 sera were collected from health participants as health control. All sera were examined by colloidal gold kits to detect the positivity of antibodies againstT.gondii. And the positivity of antibodies in sera was confirmed with ARCHITECT i2000SRsystem.ResultsThe prevalence ofT.gondiiinfection in patients was 7.06% (45/637), which was lower than the prevalence in health participants 4.88% (10/205). Among patients, 34 (5.34%) were positive only for IgG, 10 (1.57%) were only for IgM, and 1 (0.16%) was positive for both IgG and IgM. There was a significant difference in prevalence between male and female patients, but not among different age groups or diseases groups. The prevalence ofT.gondiiinfection in diseases groups varied. The prevalence was relatively high in patients with the disorders of thyroid gland and the malignant neoplasms of digestive organs, which suggests that caution should be taken to avoidT.gondiiinfection in these patients. Surprisingly, the prevalence was quite low in diffuse Large B-cell Lymphoma (DLBC) patients. This may be due to the overexpression of TNF-α in tumor tissues of DLBC patients and the higher protein level of TNF-α in sera of DLBC patients.ConclusionThis study provides a systematic exploration of the prevalence ofT.gondiiinfection in patients in a tertiary hospital. Our data contributes to a better understanding of the epidemic investigation ofT.gondiiamong patients in South China, which can help the prevention and treatment of the disease caused byT.gondiiinfection.
The possible molecular mechanism underlying the involvement of the variable shear factor QKI in the epithelial-mesenchymal transformation of oesophageal cancer
Authors: Cui Yishuang , Wu Yanan , Zhu Yingze , Liu Wei , Huang Lanxiang , Hong Ziqian , Zhang Mengshi , Zheng Xuan , Sun Guogui 
Published: July 2023

Objective
Based on the GEO, TCGA and GTEx databases, we reveal the possible molecular mechanism of the variable shear factor QKI in epithelial mesenchymal transformation (EMT) of oesophageal cancer.

Methods
Based on the TCGA and GTEx databases, the differential expression of the variable shear factor QKI in oesophageal cancer samples was analysed, and functional enrichment analysis of QKI was performed based on the TCGA-ESCA dataset. The percent-spliced in (PSI) data of oesophageal cancer samples were downloaded from the TCGASpliceSeq database, and the genes and variable splicing types that were significantly related to the expression of the variable splicing factor QKI were screened out. We further identified the significantly upregulated circRNAs and their corresponding coding genes in oesophageal cancer, screened the EMT-related genes that were significantly positively correlated with QKI expression, predicted the circRNA-miRNA binding relationship through the circBank database, predicted the miRNA-mRNA binding relationship through the TargetScan database, and finally obtained the circRNA-miRNA-mRNA network through which QKI promoted the EMT process.

Results
Compared with normal control tissue, QKI expression was significantly upregulated in tumour tissue samples of oesophageal cancer patients. High expression of QKI may promote the EMT process in oesophageal cancer. QKI promotes hsa_circ_0006646 and hsa_circ_0061395 generation by regulating the variable shear of BACH1 and PTK2. In oesophageal cancer, QKI may promote the production of the above two circRNAs by regulating variable splicing, and these circRNAs further competitively bind miRNAs to relieve the targeted inhibition of IL-11, MFAP2, MMP10, and MMP1 and finally promote the EMT process.

Conclusion
Variable shear factor QKI promotes hsa_circ_0006646 and hsa_circ_0061395 generation, and downstream related miRNAs can relieve the targeted inhibition of EMT-related genes (IL11, MFAP2, MMP10, MMP1) and promote the occurrence and development of oesophageal cancer, providing a new theoretical basis for screening prognostic markers of oesophageal cancer patients.
Alemtuzumab-induced Graves’ disease
Authors: Sheremeta M. S. , Korchagina M. O. , Guseinova R. M. , Schmidt T. E. , Nizhegorodova K. S. , Sviridenko N. Yu. , Melnichenko G. A. 
Published: July 2023

Multiple sclerosis (MS) is a severe chronic autoimmune demyelinating disease of the central nervous system, mediated by Th1/Th17 lymphocytes as well as B lymphocytes, macrophages and other immune cells. Some patients with MS are treated with alemtuzumab, a monoclonal antibody against CD52+ cells, which belongs to the disease-modifying therapies (DMTs). The main effect of alemtuzumab is related to changes in immune recruitment. Alemtuzumab therapy can induce secondary autoimmunity against the background of immune rebalancing. The thyroid gland is generally involved in the autoimmune process. Graves’ disease (GD) develops most often, followed by autoimmune thyroiditis.We present a clinical case of a patient with GD developed after alemtuzumab therapy for MS. The patient was referred to a radiologist at the Department of Radionuclide Therapy of Endocrinology Research Centre for radioiodine therapy (RAIT) due to relapse of thyrotoxicosis after anti-thyroid drug therapy for GD. The goal of treatment was achieved in 2 months, thyroid hormone therapy was initiated, against the background of this, there was compensation of thyroid function.
Zur Fortentwicklung des Raumordnungsverfahrens auch im Hinblick auf die Bestrebungen zur Beschleunigung des Planungsablaufs
Authors: Brenken Günter 
Published: July 2023

Die bundesweite Einführung des Raumordnungsverfahrens (ROV) mit erstinstanzlicher – überörtlicher – UVP durch die Novelle zum Raumordnungsgesetz (ROG) hat die Koordinierungs- und Abstimmungsaufgabe der Raumordnung wesentlich erweitert. Es gilt nun, dieses Verfahren der Prüfung des Makrostandorts raumbedeutsamer Einzelvorhaben so durchzuführen, daß die sich bietenden Verfahrensvorzüge – frühes Planungsstadium mit Änderungsmöglichkeiten auch im Grundsätzlichen, Erfassung und Erörterung aller berührten Faktoren unter Beteiligung der räumlich und fachlich befaßten Stellen – so durchzuführen, daß trotz der erweiterten Prüfungsbreite letztlich eine Verkürzung des gesamten Planungsablaufs erreicht wird. In die Abhandlung der Umweltbelange sind auch die zur Sicherung von Natur und Landschaft entwickelten Instrumente der Raumordnung einzubeziehen, was den Umwelterfordernissen im Einzelfall ein stärkeres Gewicht als bei rein fachlicher Bewertung verschaffen kann. Die Entkleidung des ROV vom nur behördeninternen Charakter durch die für die UVP vorgeschriebene Öffentlichkeitsbeteiligung läßt insbesondere bei deren erweiterter Form die Wirkung einer “Abschichtung” behandelter Aspekte geboten erscheinen. Auch für Rechtsträger, die durch das Vorhaben “betroffen” im Sinne des Verwaltungsverfahrensgesetzes sind, empfiehlt sich eine Beteiligung am ROV.
Phase Change Material on Augmentation of Fresh Water Production Using Pyramid Solar Still
Authors: Ravishankara S. , Nagarajan P.K. , Vijayakumar D. , Jawahar M.K. 
Published: July 2023

The augmentation of fresh water and increase in the solar still efficiency of a triangular pyramid is added with phase change material (PCM) on the basin. Experimental studies were conducted and the effects of production of fresh water with and without PCM were investigated. Using paraffin as the PCM material, performance of the solar still were conducted on a hot, humid climate of Chennai (13°5′ 2" North, 80°16′ 12"East), India. The use of paraffin wax increases the latent heat storage so that the energy is stored in the PCM and in the absence of solar radiation it rejects its stored heat into the basin for further evaporation of water from the basin. Temperatures of water, Tw, Temperature of phase change material, TPCM, Temperature of cover, Tc were measured using thermocouple. Results show that there is an increase of maximum 20%, in productivity of fresh water with PCM.
Weldability of high nitrogen steels: A review
Authors: Wang Xingxing , Tian Jiahao , Li Shuai , He Peng , Fang Naiwen , Wen Guodong 
Published: July 2023

Abstract
High nitrogen steel (HNS) have been widely used in many industrial fields in place of stainless steels. As we know, the welding is the main fabricating method of the HNS structural components. In this article, the recent investigations of joining methods of HNS, such as tungsten inert gas welding, melt inert-gas welding, laser welding, laser-arc hybrid welding, friction stir welding (FSW), and brazing method are summarized. First, the effect of nitrogen content in shielding gas, welding wire, and base metal on the evolution of microstructure, mechanical properties, and corrosion susceptibility of fusion welded joints are discussed systemically. Then the existing problem during FSW and brazing process of HNS are analyzed. Additionally, the key issues and future trends in the joining of HNS are proposed. The main purpose of this review is to provide a technical reference and theoretical basis for research and technological development during the welding of HNS.
Incomplete circle of Willis as a risk factor for intraoperative ischemic events during carotid endarterectomies performed under regional anesthesia – A prospective case-series
Authors: Gyöngyösi Zoltán , Belán Ivett , Nagy Edit , Fülesdi Zsófia , Farkas Orsolya , Végh Tamás , Hoksbergen Arjan Willem , Fülesdi Béla 
Published: July 2023

Abstract

Background
The role of the willisian collaterals during carotid endarterectomies (CEAs) is a debated issue. The aim of the present work was to test whether an incomplete or non-functional circle of Willis (CoW) is a risk factor for ischemic events during CEA.

Patients and methods
CEAs were performed under local anesthesia. Patients were considered symptomatic (SY) if neurological signs appeared after the cross-clamping phase. In SY patients shunt insertion was performed. CoW on CT angiograms (CTa) were analyzed offline and categorized as non-functional (missing or hypoplastic collaterals) or functional collaterals by three neuroradiologists. Near-infrared spectroscopy (NIRS) was performed throughout the procedure.

Results
Based on CTa, 67 incomplete circles were found, 54 were asymptomatic (ASY) and 13 were SY. No complete CoW was found among the SY patients. Significant differences could be detected between incomplete and complete circles between ASY and SY groups (Chi-square: 6.08; p = 0.013). The anterior communicating artery was missing or hypoplastic in 5/13 SY cases. There were no cases of the non-functional anterior communicating arteries in the ASY group (Chi-square: 32.9; p = 10−8). A missing or non-functional bilateral posterior communicating artery was observed in 9/13 SY and in 9/81 ASY patients (Chi-square: 24.4; p = 10−7). NIRS had a sensitivity of 76.9% and a specificity of 74.5% in detecting neurological symptoms.

Conclusions
Collateral ability of the CoW may be a risk factor for ischemic events during CEAs. Further studies should delineate whether the preoperative assessment of collateral capacity may be useful in decision-making about shunt use during CEA.
NR2C2 of macrophages promotes inflammation via NF-κB in LPS-induced orchitis in mice
Authors: Min Ziqian , Wan Jingyu , Xin Huan , Liu Xiaowen , Rao Xinxu , Fan Ziling , Yang Lifang , Li Dan 
Published: July 2023

In brief
Bacterial infection can induce testicular inflammation and damage male fertility. This paper reveals the role of nuclear receptor subfamily 2 group C member 2 (NR2C2) in macrophage cells in orchitis caused by bacterial endotoxin lipopolysaccharide (LPS) infection.

Abstract
Bacterial infection and induced inflammation are important causes of male infertility. Here, we described the characteristics of expression and the regulatory role of NR2C2 in testicular inflammatory injury induced by infection with the bacterial endotoxin LPS. We found that NR2C2 was highly expressed in the testes and the expression of NR2C2 was upregulated in testicular macrophages in the LPS-induced mouse orchitis model in vivo. In primary testicular macrophages and RAW264.7 cells in vitro, RNA interference with the Nr2c2 gene downregulated the expression of inflammatory factors such as IL-1β and IL-6. In addition, the knockdown of NR2C2 in macrophages alleviated the inhibitory effect of the inflammatory supernatant secreted by the macrophages on the proliferation of spermatogonia GC-1 SPG cells. Mechanistically, NR2C2 activated NF-κB signaling by binding with DR elements in the promotor of the Nfκb gene and promoted the development of inflammation. These data are the first to confirm that during LPS-induced bacterial infection, NR2C2 plays a proinflammatory role by activating IL-1β and IL-6 via the NF-κB pathway in macrophages, consequently inhibiting the proliferation of spermatogonia and damaging the quality of sperm. Our findings reveal the important role of NR2C2 in testicular inflammatory injury induced via LPS and provide a new potential target and a molecular basis for the treatment of male infertility caused by bacterial infection.