bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor immune microenvironment remodeling and prognosis of patients with esophageal squamous cell carcinoma after neoadjuvant chemotherapy with and without immunotherapy
Authors: Liu Lihong , Liu Yueping , Xu Li’ang , Ding Yan , Han Jing , Wang Qi , Chen Xiaoxi , Han Chun , Wang Lan 
Published: October 2023

Abstract
Objective This study investigated the outcomes of neoadjuvant chemotherapy with and without immunotherapy in tumor microenvironment (TME) remodeling among patients with esophageal squamous cell carcinoma (ESCC) .Methods Retrospectively reviewed the data of patients with ESCC who received neoadjuvant chemotherapy, with or without immunotherapy (nCT and nICT groups, respectively), from December 2019 to March 2022 in the Fourth Hospital of Hebei Medical University. Histopathology specimens of cancer tissue before and after treatment were examined for TME features.Results A total of 50 patients underwent R0 resection, with rates of pathological complete response (pCR) and major pathological response (MPR) of 18% and 30%, respectively. Rates of pCR were 7.1% and 22.2% (P = 0.403) and those of MPR were 7.1% and 38.9% (P = 0.028) in the nCT and nICT groups, respectively. The pCR patients had a higher baseline programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) positive expression rate than non-pCR patients (16.7% vs. 77.8%, P < 0.001). Comparing TME features before and after neoadjuvant treatment, an increase in PD-L1, CD3+ T cells, and CD8+ T cells in the tumor tissue were observed after neoadjuvant treatment, with more significantly increased in the nICT group than in the nCT group (P < 0.05). Cox regression analysis showed that pre-treatment well-differentiated tumors and positive PD-L1 were favorable factors for MPR. Post-treatment MPR was an independent factor affecting disease-free survival.Conclusion Neoadjuvant therapy could upregulate the PD-L1 expression level, increase tumor-infiltrating lymphocytes, and remodel the TME in patients with ESCC. Pre-treatment tumor differentiation and PD-L1 level could predict pathological remission.
Systems Approach in Planetary Health Education for Medical Students: A Mixed Methods Study.
Authors: Zandavalli Rafaela Brugalli , Stein Airton Tetelbom , de Camargo Tatiana Souza 
Published: October 2023

Abstract
Background
Introducing students to the "planetary health lenses" perspective is crucial. Comprehensive strategies for teaching this perspective are lacking, especially in the domains of "interconnection within nature (IWN)" and "systems thinking/complexity." There is also a scarcity of studies assessing medical students' opinions on planetary health and evaluating teaching strategies.
Objective
To understand Brazilian medical students' perceptions and knowledge of planetary health (PH) and evaluate the application of the educational material "Patient and Clinic through the Lens of Planetary Health," which addresses "IWN" and "complexity" through the sociological lens of Actor-Network Theory, in an integrative course at a medical school in Brazil.
Methods
A mixed-methods, quasi-experimental design involving two medical student classes during 2022/2023. Participants completed a questionnaire on sociodemographic data; pre- and post-intervention closed-ended questions about perceptions related to PH, and an open-ended questionnaire on experience and learning. Each student group presented a portfolio under the planetary health lenses regarding a real patient, developing a network diagram that described the social network involving both human and non-human actors with which this person is interconnected. The cohorts participated in "IWN" activities: a contemplative trail or reflection on belonging to the planet.
Results
Ninety-six students and 9 professors participated. The majority of students (66.7%) reported significant or extremely significant learning from the sessions. There was an increased perception of the need for physicians to incorporate PH into their clinical practice (p = 0.002; r = 0.46) and a heightened sense of interconnection with the environment (p = 0.003; r = 0.46). There was a gain in knowledge about how many diseases were related to PH (p < 0.02 for all 13 listed diseases). The majority (83%) found the sessions relevant or highly relevant and commented on their impact, both professionally and personally.
Conclusions
Teaching PH in a medical school allowed students to learn from the patient's perspective, considering psychosocial and environmental determinants, about the intrinsic interdependence between population health and PH. This strategy made a significant contribution by proposing pioneering didactics and offering valuable insights into the challenges and nuances of teaching PH.
Variations of plasma oxidative stress levels in male patients with chronic schizophrenia: Correlations with psychopathology and matrix metalloproteinase-9
Authors: Yang Haidong , Zhang Caiyi , Yang Man , Liu Junjun , Zhang Yuting , Liu Dongliang , Zhang Xiaobin 
Published: October 2023

Abstract
Background: Accumulating evidence has indicated that oxidative stress (OS) and matrix metalloproteinase-9 (MMP-9) may contribute to the mechanism of schizophrenia. In the present study, we aimed to evaluate the associations of OS parameters and MMP-9 levels with psychopathological symptoms in male chronic schizophrenia patients.
Methods: Plasma hydrogen peroxide (H2O2), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), serum matrix metalloproteinase-9 (MMP-9), and tissue inhibitors of metalloproteinases-1 (TIMP-1) levels were assayed in 80 male patients with chronic schizophrenia and 80 matched healthy controls. Schizophrenia symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS).
Results: Our results demonstrated that levels of antioxidant enzymes, SOD, GSH-Px, H2O2, and MDA were significantly decreased, whereas CAT and MMP-9 levels were increased in patients with schizophrenia, when compared with healthy controls (all P < 0.05). In schizophrenia patients, correlation analyses showed that H2O2 levels were significantly and positively correlated with PANSS positive scores, CAT and MDA levels were significant negatively correlated with PANSS negative scores and PANSS total scores, and MDA levels were significantly positively correlated with MMP-9 levels (all P < 0.05). However, we did not find that MMP-9 played an interaction role between OS parameters and PANSS total scores and subscales scores (all P > 0.05).
Conclusions: Our results showed that alterations of plasma OS parameters in male patients with chronic schizophrenia were associated with psychopathology and MMP-9, suggesting that OS and neuroinflammation may play important role in the mechanism of schizophrenia.
CDK10 gene mutation in a Chinese girl with Al Kaissi syndrome
Authors: Xue Xuezhen , Chen Chu'an , Wang Xiaoyan , Zheng Chunfu , Yang Wenqing 
Published: October 2023

Abstract
Background Al Kaissi syndrome is an autosomal recessive developmental disorder caused by variants in the CDK10 gene with a variable clinical presentation characterized by growth retardation, spinal deformities, especially the cervical spine, facial deformities, psychomotor development retardation with moderate to severe intellectual disability.Methods A 9 years and 5 months old Chinese girl with short stature, mental retardation, special facial features, sacral and coccygeal "Dimple"-like depression, a slightly smaller pituitary gland, and cervical spine deformity was diagnosed with Al Kaissi syndrome by whole-exome sequencing showing a CDK10 gene mutation.Results Gene sequencing results showed that the child had a heterozygous mutation c.739C > T (p.Q247X) (NM_052988 exon 10) and a mutation c.663C > G > T (p.D221E) (NM_052988 exon 9) in the CDK10 gene. The compound heterozygous mutation was verified by one generation of the family. This conforms to the recessive inheritance pattern of the disease. The associated disease is consistent with the clinical manifestations of the patient. The compound heterozygous mutation can lead to the occurrence of the disease.Conclusion The first case of Al Kaissi syndrome reported in China expands the phenotypic and genotypic spectrum of Al Kaissi syndrome.
Targeted and Localized Cancer Drug Release Kinetics from Microporous Poly-di-methyl-siloxane (PDMS) Devices: in-vivo Studies for the Treatment of Triple Negative Breast Cancer
Authors: Eluu Stanley , Yiporo Danyuo , Salifu Ali , Obayemi John , Oko Augustine , Aina Toyin , Oparah Josephine , Ezeala Chukwudi , Etinosa Precious , Ugwu Chigozie , Esimone Charles , Soboyejo Winston 
Published: October 2023

Abstract
Triple-negative breast cancer (TNBC) treatment is challenging and frequently characterized by an aggressive phenotype and low prognosis in comparison to other subtypes. This paper presents an implantable microporous poly-di-methyl-siloxane device for the delivery of targeted therapeutic agents (LHRH-paclitaxel and LHRH-prodigiosin) for the treatment and possible prevention of triple-negative cancer recurrence. The possible cytotoxic effects of the drugs on liver, kidney, and lung tissues are also assessed. Drug-loaded implantable microporous poly-di-methyl-siloxane (PDMS) devices were fabricated. Subcutaneous triple-negative xenograft breast tumors were then induced in athymic female nude mice that were four weeks old. Two weeks later, the tumors were surgically removed, and the device implanted. Mice were observed for tumor regrowth and organ toxicity. In addition, the cytotoxic response was assessed in vitro using the Alamar blue assay. The animal study revealed that there was no tumor regrowth, six weeks post-treatment, when the LHRH targeted drugs (LHRH-paclitaxel and LHRH-prodigiosin) were used for the treatment. It was also noted that the targeted cancer drugs did not induce any adverse effect on the liver, kidneys, or lungs, based on the results of the quantitative and qualitative toxicity studies. Furthermore, the outcomes of the in vitro assessment demonstrated a significant reduction (P < 0.05) in percentage cell growth inhibition in a time-dependent manner in the groups treated with PG, PG-LHRH, PTX, and PTX-LHRH. The implications of the results are discussed for the targeted and localized treatment of triple negative breast cancer.
Designing of drug imprinted polymeric microcryogels for controlled release of Darunavir
Authors: Safak Ismet , Çalışır Merve , Bakhshpour-Yucel Monireh , Sağlam Necdet , Denizli Adil 
Published: October 2023

Abstract
Darunavir (D.V) is a pivotal antiretroviral medication designed to combat viruses with prolonged treatment requirements, notably gaining recognition as one of the primary choices for treating AIDS, a disease caused by the human immunodeficiency virus (HIV). Bio polymeric materials like microcryogels become the center of attention in most research areas such as controlled release systems. These systems offer the advantage of precise drug administration, ensuring effective therapeutic outcomes through the delivery of specific drug doses. Microcryogels, characterized by their super macroporous, elastic, and spongy morphology, have emerged as a focal point in biomedical applications, particularly when combined with molecularly imprinted polymers (MIPs). In this study, the controlled release and kinetics studies of the D.V were investigated with the D.V imprinted poly (2-hydroxyethyl methacrylate) (pHEMA) based microcryogels. D.V imprinted pHEMA microcryogels with different cross-linker ratios and different loaded drugs were prepared for studies of in vitro release of D.V scanning electron microscopy (SEM), Brunauer–Emmett–Teller (BET) and Fourier transform infrared spectroscopy (FTIR) methods have been considered suitable for the characterization of cryogels that have been designed and whose sensitivity has been enhanced by molecular imprinting. Cytotoxicity of D.V imprinted microcryogels was also inspected using mouse fibroblast cell line L929. The comprehensive analysis results underscore the potential of these meticulously designed microcryogels, showcasing their utility in medical applications. Notably, these microcryogels exhibited controlled drug release, with efficiency levels of up to 85% and a sustained release duration of 40 hours, positioning them as a valuable option for advanced drug delivery systems in the medical field.
Effect and potential mechanism of p75NTR in the regulation of the circadian rhythm and daily mineralization during tooth development
Authors: Song Jinlin , Zhao Manzhu , Yuan Hongyan , Wang Di , Li Meng , Xie Bo , Zhou Xuqiang , Lu Mingjie , Qiu Ye 
Published: October 2023

Abstract

Circadian rhythms are innate processes that are responsive to light/dark cycles and participate in the regulation of various physiological functions. Mammalian teeth provide a precise record of these rhythms through the incremental growth lines in the dentine and enamel. The aim of this study was to identify the effect and potential mechanism of p75 neurotrophin receptor (p75NTR) in the regulation of the circadian rhythm and daily mineralization during tooth development. p75NTR expression was found to be similar to that of the clock genes and mineralization-related factors in rat dental germs. The significant decreases in the body size and weight of p75NTR knock-out mice indicated that p75NTR might promote osteogenesis. p75NTR showed close positive relationships with melatonin, crown length, eruption speed, and daily mineralization width. In the circadian rhythm dynamics of rat dental germs study, p75NTR oscillated regularly at an approximately 24-hour interval, at both the mRNA and protein levels; this was similar to most clock genes (Bmal1, Clock, Per1, and Per2), mineralization-related genes (Runx2, ALP), and odontogenesis-related genes (Msx1, Dlx1, Dmp1 and Dspp). Moreover, p75NTR displayed positive relationships with clock, mineralization-related, and odontogenesis-related genes in both the over-expression and knockdown experiments. These data reveal that p75NTR promotes the crown length, eruption speed, and daily mineralization width and significantly affects the circadian rhythm and periodic mineralization during tooth development. Furthermore, CK2 was found to be a possible downstream factor of p75NTR; however, direct bonding between CK2 and p75NTR was not observed. Further studies are needed to verify these findings.
A Rare Clinical Scenario: Arteriovenous Fistula Secondary to Deep Vein Thrombosis Complicated with Distal Arterial Stenosis
Authors: Chen Junjie , Lai Zhichao , Chen Yuexin 
Published: October 2023

Abstract
Background: The purpose of this study was to report the successful treatment of a case of arteriovenous fistula secondary to deep vein thrombosis complicated byatherosclerosis of the distal artery, which was a quite rare scenario without consensus for clinical treatment.
Case presentation: A 76-year-old woman presented with severe edema and recurrent ulcers in his lower right extremity that had developed for approximately 4 years. His symptoms worsened 2 years ago because of deep vein thrombosis and were not mitigated after the implantation of an inferior vena cava filter followed by standard anticoagulant treatment. Computed tomography (CT) revealed a postthrombotic obstruction of his external iliac veins and a distal arterial stenosis due to atherosclerosis as well as several arteriovenous fistulas between thefemoral vein, femoral artery and their branches. Endovascular recanalization of stenosis and occlusion by balloon dilation resulted in significant improvement of clinical symptoms. Interestingly, arterial patency seems more important than venous patencyin the process of symptomatic relief.
Conclusion: Arteriovenous fistula in the lower extremities may develop following deep vein thrombosis and be exacerbated by occlusion or stenosis of the distal artery. Recanalization is a more recommended treatment option according to available data thus far.
Drought and wetness periods in Iran under the influences of subtropical sea surface temperature anomalies and large scale atmospheric circulation
Authors: mirzaei Nabi , Hejazizadeh Zahra , Darand Mohammad , Mohammadi Bakhtiyar , Naserzadeh Mohammad Hossein , Alijani Bohloul 
Published: October 2023

Abstract
In this study, Drought and wetness periods in Iran under the influences of sea surface temperature (SST) anomalies and large scale atmospheric circulation, were studied using the SPI from 1979 to 2020. To illustrate changes in atmospheric circulation patterns, sinuosity, humidity, jet stream and u, v were analyzed. Severe droughts in autumn (OND) are associated with negative SST anomalies in the North Atlantic, the Caspian Sea, Western Mediterranean and Oman Sea that affect the drought through decreasing atmospheric humidity and strengthening high pressure. Wetness are also associated with positive SST anomalies in the Mediterranean, North Atlantic and Black Sea. These conditions are associated to the positive SST anomaly over the region (-80° W to 70° E, 10° N to 60° N) in winter (JFM).In some cases, the drought occurred simultaneously with the positive temperature anomaly in the Mediterranean and Persian Gulf. Importantly, a large proportion of the wet periods during JFM were associated with positive SST anomalies in the North Atlantic, the Oman Sea, and the western Mediterranean. The increase in SST occurred simultaneously with the increase in precipitation in October and November from 1979 to 2010, while decrease in JFM precipitation was observed. Precipitation anomaly is associated with the position of jet stream centers. Wetness occur when the jet stream is located over Southern Mediterranean and the Arabian Peninsula. The pattern revealed that the occurrence of severe droughts is related to jet stream and it’s the retreated toward the west that leads to the reduction of westerlies waves.
An improved anticancer effect of 5-fluorouracil (5-FU) in combination with Prodigiosin
Authors: ELGHALI Fares , MSALBI Dhouha , SAHLI Emna , HAKIM Bochra , MNIF sAMI , AIFA Mohamed Sami 
Published: October 2023

Abstract

5-fluorouracil (5-FU) is the standard of care therapy for colorectal cancer. However, complex 5-FU resistance mechanisms limit the success of this approach. Prodigiosin (PG), a secondary metabolite from various bacteria, exerts different biological activities including cancer-preventive and anticancer effects. However, studies on the anticancer effects and underlying mechanisms of PG in human colorectal and lung cancer are still limited. The present study is conducted to investigate the anticancer properties and/or adjuvant chemotherapy of PG in human colorectal and lung cancer. Cell lines HCT116, LoVo and A549 were treated with different concentrations of PG. The antiproliferative effects of PG were measured, and the apoptosis and cell cycle dynamics were assessed by flow cytometry. Our results showed that PG effectively inhibited cell proliferation and induced apoptosis. In combinatory treatment, based on PG and 5-FU, we observed a clear improvement in tumor cell proliferation inhibition. In fact, the percentage of cells in the G0/G1 phase was higher and the percentage of cells in the S phase was lower compared to treated cells separately by PG and 5-FU in all the used cell lines. Our docking studies supported targeting Akt1 by PG which could explain its proapoptotic effect separately or in combination with 5-Fu. PG obviously inhibited the tumor growth and enhanced the 5-FU therapeutic efficacy in HCT116, LoVo and A549 cells. Taken together, our findings highlight that PG effectively inhibited the growth of tumor and enhanced the sensitivity to thermotherapy, indicating PG is an inhibitor of Akt1.
Validation of Low-cost Reflectometer to Identify Phytochemical Accumulation in Food Crops
Authors: Rosier Carl , Kittredge Dan , Nainiger Barbara , Duarte Octavio , Austic Greg , TerAvest Dan 
Published: October 2023

Abstract
Diets consisting of greater quantity/diversity of phytochemicals are correlated with reduced risk of disease. This understanding guides policy development increasing awareness of the importance of consuming fruits, grains, and vegetables. Enacted policies presume uniform concentrations of phytochemicals across crop varieties regardless of production/harvesting methods. A growing body of research suggests that concentrations of phytochemicals can fluctuate within crop varieties. Improved awareness of how cropping practices influence phytochemical concentrations are required, guiding policy development improving human health. Reliable, inexpensive laboratory equipment represents one of several barriers limiting further study of the complex interactions influencing crop phytochemical accumulation. Addressing this limitation our study validated the capacity of a low-cost Reflectometer ($500) to measure phytochemical content in selected crops, against a commercial grade laboratory spectrophotometer. Our results suggest the Reflectometer provides an accurate accounting of phytochemical content within evaluated crops. Additionally, we confirmed large variation in phytochemical content within specific crop varieties, suggesting that cultivar is but one of multiple drivers of phytochemical accumulation. Our findings indicate dramatic nutrient variations could exist across the food supply, a point whose implications are not well understood. Future studies should investigate the interactions between crop phytochemical accumulation and farm management practices that influence specific soil characteristics.
High tibial osteotomy combined with platelet-rich plasma for knee osteoarthritis: A Systematic review and Meta-analysis
Authors: Zhang Wenbin , Ma Yulin , Song Hao , Lu Feilong , Hu Yimei 
Published: October 2023

Abstract
Objective: To systematically review the clinical efficacy and safety of high tibial osteotomy combined with platelet-rich plasma in treating knee osteoarthritis, and provide evidence-based medical evidence for its effectiveness in treating knee osteoarthritis.
Methods: Clinical studies of high tibial osteotomy combined with platelet-rich plasma for knee osteoarthritis, before June 2023, were searched in databases. Strictly screen out the literature that meets the inclusion criteria, extract the literature data information, and input it into RevMan5.4 for analysis.
Results: 10 studies(12 controls) were included, with 625 patients. The results showed that, in general, VAS(MD=-0.53，95%CI(-0.76,-0.31), P＜0.00001), ROM(MD=7.24,95%CI(2.79,11.69), P=0.001), WOMAC(MD=-6.91,95%CI(-9.47,-4.34), P＜0.00001), cartilage recovery(cartilage thickness: MD=0.43, 95%CI(0.35, 0.51), P<0.00001; cartilage regeneration: RR=1.81, 95%CI(1.40, 2.33), P<0.00001; ICRS grade: RR=1.96, 95%CI(1.44, 2.66), P<0.0001), and Lysholm(MD=6.51, 95%CI(4.97, 8.04), P<0.00001) after PRP treatment had significant advantages compared with the control group. After treatment, there was no statistically significant difference of knee joint mechanical axes angles in platelet-rich plasma group compared with control group (FTA: MD=-0.29, 95%CI(-1.07, 0.49), P=0.47; MPTA: MD=0.19, 95%CI(-0.49, 0.88), P=0.58; PTS: MD=-0.12, 95%CI(-0.49, 0.25), P=0.53; KVA: MD=-0.30, 95%CI(-1.77, 1.17), P=0.69; WBL: MD=1.10, 95%CI(-0.89, 3.09), P=0.28).
Conclusion: The results showed that in the treatment of KOA by HTO, the combined PRP group had better efficacy than other control groups, and had certain safety reliability.