bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting KRASG12V mutations with HLA class II-restricted TCR for the immunotherapy in solid tumors
Authors: Ai Qi , Li Fanlu , Zou Siyi , Zhang Zehui , Jin Yangbing , Jiang Lingxi , Chen Hao , Deng Xiaxing , Peng Chenghong , Mou Nan , Wen Chenlei , Shen Baiyong , Zhan Qian
Published: May 2023

KRAS mutation is a significant driving factor of tumor, and KRASG12V mutation has the highest incidence in solid tumors such as pancreatic cancer and colorectal cancer. Thus, KRASG12V neoantigen-specific TCR-engineered T cells could be a promising cancer treatment approach for pancreatic cancer. Previous studies had reported that KRASG12V-reactive TCRs originated from patients’ TILs could recognized KRASG12V neoantigen presented by specific HLA subtypes and remove tumor persistently in vitro and in vivo. However, TCR drugs are different from antibody drugs in that they are HLA-restricted. The different ethnic distribution of HLA greatly limits the applicability of TCR drugs in Chinese population. In this study, we have identified a KRASG12V-specific TCR which recognized classII MHC from a colorectal cancer patient. Interestingly, we observed that KRASG12V-specific TCR-engineered CD4+ T cells, not CD8+ T cells, demonstrated significant efficacy in vitro and in xenograft mouse model, exhibiting stable expression and targeting specificity of TCR when co-cultured with APCs presenting KRASG12V peptides. TCR-engineered CD4+ T cells were co-cultured with APCs loaded with neoantigen, and then HLA subtypes were identified by the secretion of IFN-γ. Collectively, our data suggest that TCR-engineered CD4+ T cells can be used to target KRASG12V mutation presented by HLA-DPB1*03:01 and DPB1*14:01, which provide a high population coverage and are more suitable for the clinical transformation for Chinese, and mediate tumor killing effect like CD8+ T cells. This TCR hold promise for precision therapy in immunotherapy of solid tumors as an attractive candidate.
Insights into anti-tumor immunity via the polyomavirus shared across human Merkel cell carcinomas
Authors: Jani Saumya , Church Candice D. , Nghiem Paul
Published: May 2023

Understanding and augmenting cancer-specific immunity is impeded by the fact that most tumors are driven by patient-specific mutations that encode unique antigenic epitopes. The shared antigens in virus-driven tumors can help overcome this limitation. Merkel cell carcinoma (MCC) is a particularly interesting tumor immunity model because (1) 80% of cases are driven by Merkel cell polyomavirus (MCPyV) oncoproteins that must be continually expressed for tumor survival; (2) MCPyV oncoproteins are only ~400 amino acids in length and are essentially invariant between tumors; (3) MCPyV-specific T cell responses are robust and strongly linked to patient outcomes; (4) anti-MCPyV antibodies reliably increase with MCC recurrence, forming the basis of a standard clinical surveillance test; and (5) MCC has one of the highest response rates to PD-1 pathway blockade among all solid cancers. Leveraging these well-defined viral oncoproteins, a set of tools that includes over 20 peptide-MHC class I tetramers has been developed to facilitate the study of anti-tumor immunity across MCC patients. Additionally, the highly immunogenic nature of MCPyV oncoproteins forces MCC tumors to develop robust immune evasion mechanisms to survive. Indeed, several immune evasion mechanisms are active in MCC, including transcriptional downregulation of MHC expression by tumor cells and upregulation of inhibitory molecules including PD-L1 and immunosuppressive cytokines. About half of patients with advanced MCC do not persistently benefit from PD-1 pathway blockade. Herein, we (1) summarize the lessons learned from studying the anti-tumor T cell response to virus-positive MCC; (2) review immune evasion mechanisms in MCC; (3) review mechanisms of resistance to immune-based therapies in MCC and other cancers; and (4) discuss how recently developed tools can be used to address open questions in cancer immunotherapy. We believe detailed investigation of this model cancer will provide insight into tumor immunity that will likely also be applicable to more common cancers without shared tumor antigens.
Cognitive impairment in long-COVID and its association with persistent dysregulation in inflammatory markers
Authors: Damiano Rodolfo Furlan , Rocca Cristiana Castanho de Almeida , Serafim Antonio de Pádua , Loftis Jennifer M. , Talib Leda Leme , Pan Pedro Mário , Cunha-Neto Edecio , Kalil Jorge , de Castro Gabriela Salim , Seelaender Marilia , Guedes Bruno F. , Nagahashi Marie Suely K. , de Souza Heraldo Possolo , Nitrini Ricardo , Miguel Euripedes Constantino , Busatto Geraldo , Forlenza Orestes V. ,   HCFMUSP COVID-19 Study Group
Published: May 2023

Objective

To analyze the potential impact of sociodemographic, clinical and biological factors on the long-term cognitive outcome of patients who survived moderate and severe forms of COVID-19.

Methods

We assessed 710 adult participants (Mean age = 55 ± 14; 48.3% were female) 6 to 11 months after hospital discharge with a complete cognitive battery, as well as a psychiatric, clinical and laboratory evaluation. A large set of inferential statistical methods was used to predict potential variables associated with any long-term cognitive impairment, with a focus on a panel of 28 cytokines and other blood inflammatory and disease severity markers.

Results

Concerning the subjective assessment of cognitive performance, 36.1% reported a slightly poorer overall cognitive performance, and 14.6% reported being severely impacted, compared to their pre-COVID-19 status. Multivariate analysis found sex, age, ethnicity, education, comorbidity, frailty and physical activity associated with general cognition. A bivariate analysis found that G-CSF, IFN-alfa2, IL13, IL15, IL1.RA, EL1.alfa, IL45, IL5, IL6, IL7, TNF-Beta, VEGF, Follow-up C-Reactive Protein, and Follow-up D-Dimer were significantly (p<.05) associated with general cognition. However, a LASSO regression that included all follow-up variables, inflammatory markers and cytokines did not support these findings.

Conclusion

Though we identified several sociodemographic characteristics that might protect against cognitive impairment following SARS-CoV-2 infection, our data do not support a prominent role for clinical status (both during acute and long-stage of COVID-19) or inflammatory background (also during acute and long-stage of COVID-19) to explain the cognitive deficits that can follow COVID-19 infection.
Lack of strong innate immune reactivity renders macrophages alone unable to control productive Varicella-Zoster Virus infection in an isogenic human iPSC-derived neuronal co-culture model
Authors: Van Breedam Elise , Buyle-Huybrecht Tamariche , Govaerts Jonas , Meysman Pieter , Bours Andrea , Boeren Marlies , Di Stefano Julia , Caers Thalissa , De Reu Hans , Dirkx Laura , Schippers Jolien , Bartholomeus Esther , Lebrun Marielle , Sadzot-Delvaux Catherine , Rybakowska Paulina , Alarcón-Riquelme Marta E. , Marañón Concepción , Laukens Kris , Delputte Peter , Ogunjimi Benson , Ponsaerts Peter
Published: May 2023

With Varicella-Zoster Virus (VZV) being an exclusive human pathogen, human induced pluripotent stem cell (hiPSC)-derived neural cell culture models are an emerging tool to investigate VZV neuro-immune interactions. Using a compartmentalized hiPSC-derived neuronal model allowing axonal VZV infection, we previously demonstrated that paracrine interferon (IFN)-α2 signalling is required to activate a broad spectrum of interferon-stimulated genes able to counteract a productive VZV infection in hiPSC-neurons. In this new study, we now investigated whether innate immune signalling by VZV-challenged macrophages was able to orchestrate an antiviral immune response in VZV-infected hiPSC-neurons. In order to establish an isogenic hiPSC-neuron/hiPSC-macrophage co-culture model, hiPSC-macrophages were generated and characterised for phenotype, gene expression, cytokine production and phagocytic capacity. Even though immunological competence of hiPSC-macrophages was shown following stimulation with the poly(dA:dT) or treatment with IFN-α2, hiPSC-macrophages in co-culture with VZV-infected hiPSC-neurons were unable to mount an antiviral immune response capable of suppressing a productive neuronal VZV infection. Subsequently, a comprehensive RNA-Seq analysis confirmed the lack of strong immune responsiveness by hiPSC-neurons and hiPSC-macrophages upon, respectively, VZV infection or challenge. This may suggest the need of other cell types, like T-cells or other innate immune cells, to (co-)orchestrate an efficient antiviral immune response against VZV-infected neurons.
Simultaneous co-infection with swine influenza A and porcine reproductive and respiratory syndrome viruses potentiates adaptive immune responses
Authors: Chrun Tiphany , Maze Emmanuel A. , Roper Kelly J. , Vatzia Eleni , Paudyal Basudev , McNee Adam , Martini Veronica , Manjegowda Tanuja , Freimanis Graham , Silesian Adrian , Polo Noemi , Clark Becky , Besell Emily , Booth Georges , Carr Brigid Veronica , Edmans Matthew , Nunez Alejandro , Koonpaew Surapong , Wanasen Nanchaya , Graham Simon P. , Tchilian Elma
Published: May 2023

Porcine respiratory disease is multifactorial and most commonly involves pathogen co-infections. Major contributors include swine influenza A (swIAV) and porcine reproductive and respiratory syndrome (PRRSV) viruses. Experimental co-infection studies with these two viruses have shown that clinical outcomes can be exacerbated, but how innate and adaptive immune responses contribute to pathogenesis and pathogen control has not been thoroughly evaluated. We investigated immune responses following experimental simultaneous co-infection of pigs with swIAV H3N2 and PRRSV-2. Our results indicated that clinical disease was not significantly exacerbated, and swIAV H3N2 viral load was reduced in the lung of the co-infected animals. PRRSV-2/swIAV H3N2 co-infection did not impair the development of virus-specific adaptive immune responses. swIAV H3N2-specific IgG serum titers and PRRSV-2-specific CD8β+T-cell responses in blood were enhanced. Higher proportions of polyfunctional CD8β+T-cell subset in both blood and lung washes were found in PRRSV-2/swIAV H3N2 co-infected animals compared to the single-infected groups. Our findings provide evidence that systemic and local host immune responses are not negatively affected by simultaneous swIAV H3N2/PRRSV-2 co-infection, raising questions as to the mechanisms involved in disease modulation.
Use of an earthen clay pot refrigerator with a thermoelectric cooler for extending farm produce shelf life
Authors: Patel Nishigandha Sandeep , Pawar Sachin , Bhojwani Virendra
Published: May 2023

Conventional cold storage systems increase the risk of damage and are no longer used for the long-term storage of agricultural products. Thus, newer affordable and energy-efficient storage systems are required for enhancing the shelf life of farm produce. We investigated the coefficient of performance (COP) of an earthen clay pot refrigerator with a thermoelectric cooler (TEC) and explored cooling strategies to enhance cooling and electrical performance for increasing the shelf life of farm produce. We used MATLAB Simulink to analyze Peltier TEC module efficiency. The intrinsic characteristics, including the Seebeck coefficient (α), thermal conductivity (K), and electrical resistance (R), were determined, forming the basis of the Peltier module in MATLAB Simulink. Thermal characteristics such as COP and cooling capacity were studied as a function of system voltage (Vin) and current (Iin). The model was equipped with a 12 V/6 A, 60 W TEC and was verified by simulation investigation. We also used psychrometric measures (e.g., wet bulb, dry bulb, and dew point temperatures and relative humidity) to determine the extent of wetness or dryness of an object and monitor other temperatures of the clay pot refrigerator. The results revealed that the ambient temperature and cold and hot side temperatures fundamentally affected TEC performance. The TEC extended the shelf life of tomatoes, potatoes, and spinach by 60% compared to those stored under ambient conditions, thereby reducing their wastage. In conclusion, earthen refrigeration using TEC doubled the shelf life of farm produce compared to storage under ambient conditions, saving money, resources, labor, and supplies and enabling the development of efficient and environmentally friendly refrigeration systems.
Non-cirrhotic portal hypertension secondary to cholangiointestinal anastomotic stricture after choledochal cyst excision: a case report
Authors: Zhang Xu , Yan Jun Qing , Gao Yan Ying , Song De Zhao , Lou Cheng
Published: May 2023

Background

Cystectomy accompanied by biliary system reconstruction is an important treatment option for choledochal cysts, but the risk of post-operative complications is high. The most famous long-term complication is anastomotic stricture, whereas non-cirrhotic portal hypertension secondary to cholangiointestinal anastomotic stricture is rare.

Case summary

Here we report the case of a 33-year-old female patient with a type I choledochal cyst who underwent choledochal cyst excision with Roux-en-Y hepaticojejunostomy. Thirteen years later, the patient presented with severe esophageal and gastric variceal bleeding, splenomegaly, and hypersplenism. Furthermore, cholangiointestinal anastomotic stricture with cholangiectasis was identified on imaging. A pathological examination of the liver suggested intrahepatic cholestasis, but the fibrosis was mild and inconsistent with severe portal hypertension. Therefore, the final diagnosis was portal hypertension secondary to a cholangiointestinal anastomotic stricture after choledochal cyst surgery. Fortunately, the patient recovered well after endoscopic treatment and dilated cholangiointestinal anastomotic stricture.

Conclusion

Choledochal cyst excision with Roux-en-Y hepaticojejunostomy is the recommended standard of care for type I choledochal cysts; however, the long-term risk of cholangiointestinal anastomotic stricture requires consideration. Moreover, cholangiointestinal anastomotic stricture can lead to portal hypertension, and the degree of elevated portal pressure may be inconsistent with the degree of intrahepatic fibrosis.
Efficacy and safety of anti-vascular endothelial growth factor agents in the treatment of primary pterygium
Authors: Zhang Bowen , Dong Xingmei , Sun Yi
Published: May 2023

Purpose

To further evaluate the efficacy and safety of anti-vascular endothelial growth factor (VEGF) agents in management of primary pterygium.

Methods

Randomized controlled trials (RCTs) in databases of PubMed, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception to September 2022. Recurrences and complications were evaluated as the pooled risk ratio (RR) and 95% confidence interval (CI) using random-effects model.

Results

In total of 1,096 eyes in 19 RCTs were included. Anti-VEGF agents statistically decreased recurrence rate of pterygium following surgery (RR 0.47, 95% CI 0.31–0.74, P < 0.001). Subgroup analysis showed that anti-VEGF as an adjunct to bare sclera (RR 0.34, 95% CI 0.13–0.90, P = 0.03) and conjunctival autograft (RR 0.50, 95% CI 0.26–0.96, P = 0.04) statistically reduced recurrence rate, while the effect was not favorable for conjunctivo-limbo autograft (RR 0.99, 95% CI 0.36–2.68, P = 0.98). Anti-VEGF agents statistically decreased recurrence in White patients (RR 0.48, 95% CI 0.28–0.83, P = 0.008), while didn't in Yellow patients (RR 0.43, 95% CI 0.12–1.47, P = 0.18). Both topical (RR 0.19, 95% CI 0.08–0.45, P < 0.001) and subconjunctival anti-VEGF agents (RR 0.64, 95% CI 0.45–0.91, P = 0.01) had a positive influence on recurrence. There was no statistically significant difference in complications between the groups (RR 0.80, 95% CI 0.52–1.22, P = 0.29).

Conclusions

As adjuvant treatment, anti-VEGF agents statistically reduced the recurrence following pterygium surgery, especially among White patients. Anti-VEGF agents were well tolerated without increased complications.
Gene expression and locomotor recovery in adult rats with spinal cord injury and plasma-synthesized polypyrrole/iodine application combined with a mixed rehabilitation scheme
Authors: Coyoy-Salgado Angélica , Orozco-Barrios Carlos , Sánchez-Torres Stephanie , Olayo María Guadalupe , Cruz Guillermo Jesus , Morales-Corona Juan , Olayo Roberto , Diaz-Ruiz Araceli , Ríos Camilo , Alvarez-Mejia Laura , Mondragón-Lozano Rodrigo , Morales-Guadarrama Axayacatl , Alonso-García Ana Lucía , Fabela-Sánchez Omar , Salgado-Ceballos Hermelinda
Published: May 2023

Introduction

Spinal cord injury (SCI) can cause paralysis, for which effective therapeutic strategies have not been developed yet. The only accepted strategy for patients is rehabilitation (RB), although this does not allow complete recovery of lost functions, which makes it necessary to combine it with strategies such as plasma-synthesized polypyrrole/iodine (PPy/I), a biopolymer with different physicochemical properties than PPy synthesized by conventional methods. After SCI in rats, PPy/I promotes functional recovery. Therefore, the purpose of this study was to increase the beneficial effects of both strategies and identify which genes activate PPy/I when applied alone or in combination with a mixed scheme of RB by swimming and enriched environment (SW/EE) in rats with SCI.

Methods

Microarray analysis was performed to identify mechanisms of action underlying the effects of PPy/I and PPy/I+SW/EE on motor function recovery as evaluated by the BBB scale.

Results

Results showed robust upregulation by PPy/I in genes related to the developmental process, biogenesis, synapse, and synaptic vesicle trafficking. In addition, PPy/I+SW/EE increased the expression of genes related to proliferation, biogenesis, cell development, morphogenesis, cell differentiation, neurogenesis, neuron development, and synapse formation processes. Immunofluorescence analysis showed the expression of β-III tubulin in all groups, a decreased expression of caspase-3 in the PPy/I group and GFAP in the PPy/I+SW/EE group (p < 0.05). Better preservation of nerve tissue was observed in PPy/I and PPy/SW/EE groups (p < 0.05). In the BBB scale, the control group scored 1.72 ± 0.41, animals with PPy/I treatment scored 4.23 ± 0.33, and those with PPy/I+SW/EE scored 9.13 ± 0.43 1 month after follow-up.

Conclusion

Thus, PPy/I+SW/EE could represent a therapeutic alternative for motor function recovery after SCI.
Association between functional disability with postural balance among patients with chronic low back pain
Authors: Sun Pingge , Li Kunbin , Yao Xianli , Wu Zhiyuan , Yang Yafei
Published: May 2023

Introduction

Postural balance is impaired in patients with chronic low back pain (CLBP). In addition, the swaying velocity can be aﬀected by low back pain (LBP) dysfunction. However, the extent to which the dysfunction aﬀects postural balance in CLBP patients remains unclear. Therefore, this study aimed to investigate the eﬀect of LBP-related disability on postural balance among CLBP patients and determine factors associated with postural balance impairments.

Methods

Participants with CLBP were recruited and instructed to complete the one-leg stance and Y-balance test. Moreover, they were divided into two subgroups (i.e., low and medium to high LBP-related disability groups) to compare the diﬀerence in postural balance based on the degree of LBP-related disability measured by the Roland Morris Disability Questionnaire. The relationships between postural balance and negative emotions as well as LBP characteristics were determined using the Spearman correlations.

Results

A total of 49 participants with low LBP-related disabilities and 33 participants with medium to high LBP-related disabilities participated in the study. Compared to the medium to high LBP-related disability group, patients in the low LBP-related disability group performed better in one-leg stance on the left leg (z = -2.081, p = 0.037). For Y-balance test, patients in the low LBP-related disability group also had greater normalized values of left leg reach in posteromedial (t = 2.108, p = 0.038) direction and composite score (t = 2.261, p = 0.026) and of right leg reach in posteromedial (t = 2.185, p = 0.032), and posterolateral (t = 2.137, p = 0.036) directions as well as composite score (t = 2.258, p = 0.027). Factors associated with postural balance impairments were also revealed, such as anxiety, depression, and fear avoidance belief.

Discussion

The greater the dysfunction degree, the worse the CLBP patient’s postural balance impairment. Negative emotions could also be considered contributing factors for postural balance impairments.
Estimation of brain tissue response by electrical stimulation in a subject-specific model implemented by conductivity tensor imaging
Authors: Katoch Nitish , Kim Youngsung , Choi Bup Kyung , Ha Sang Woo , Kim Tae Hoon , Yoon Eun Ju , Song Sang Gook , Kim Jin Woong , Kim Hyung Joong
Published: May 2023

Electrical stimulation such as transcranial direct current stimulation (tDCS) is widely used to treat neuropsychiatric diseases and neurological disorders. Computational modeling is an important approach to understand the mechanisms underlying tDCS and optimize treatment planning. When applying computational modeling to treatment planning, uncertainties exist due to insufficient conductivity information inside the brain. In this feasibility study, we performed in vivo MR-based conductivity tensor imaging (CTI) experiments on the entire brain to precisely estimate the tissue response to the electrical stimulation. A recent CTI method was applied to obtain low-frequency conductivity tensor images. Subject-specific three-dimensional finite element models (FEMs) of the head were implemented by segmenting anatomical MR images and integrating a conductivity tensor distribution. The electric field and current density of brain tissues following electrical stimulation were calculated using a conductivity tensor-based model and compared to results using an isotropic conductivity model from literature values. The current density by the conductivity tensor was different from the isotropic conductivity model, with an average relative difference |rD| of 52 to 73%, respectively, across two normal volunteers. When applied to two tDCS electrode montages of C3-FP2 and F4-F3, the current density showed a focused distribution with high signal intensity which is consistent with the current flowing from the anode to the cathode electrodes through the white matter. The gray matter tended to carry larger amounts of current densities regardless of directional information. We suggest this CTI-based subject-specific model can provide detailed information on tissue responses for personalized tDCS treatment planning.
The role of intestinal microbiota and microRNAs in the anti-inflammatory effects of cranberry: from pre-clinical to clinical studies
Authors: Taibi Amel , Lofft Zoe , Laytouni-Imbriaco Bianca , Comelli Elena Maria
Published: May 2023

Cranberries have known anti-inflammatory properties, which extend their benefits in the context of several chronic diseases. These benefits highly rely on the polyphenol profile of cranberries, one of few foods rich in A-type proanthocyanidin (PAC). A-type PAC comprises flavan-3-ol subunits with an additional interflavan ether bond in the conformational structure of the molecule, separating them from the more commonly found B-type PAC. PACs with a degree of polymerization higher than three are known to reach the colon intact, where they can be catabolyzed by the gut microbiota and biotransformed into lower molecular weight organic acids that are available for host absorption. Gut microbiota-derived metabolites have garnered much attention in the past decade as mediators of the health effects of parent compounds. Though, the mechanisms underlying this phenomenon remain underexplored. In this review, we highlight emerging evidence that postulates that polyphenols, including ones derived from cranberries, and their metabolites could exert anti-inflammatory effects by modulating host microRNAs. Our review first describes the chemical structure of cranberry PACs and a pathway for how they are biotransformed by the gut microbiota. We then provide a brief overview of the benefits of microbial metabolites of cranberry in the intestinal tract, at homeostasis and in inflammatory conditions. Finally, we discuss the role of microRNAs in intestinal health and in response to cranberry PAC and how they could be used as targets for the maintenance of intestinal homeostasis. Most of this research is pre-clinical and we recognize that conducting clinical trials in this context has been hampered by the lack of reliable biomarkers. Our review discusses the use of miRNA as biomarkers in this context.
Case Report: Paraganglioma in the sellar region: longitudinal observation and surgical outcome
Authors: Wang Yingjie , Yang Xuan , Ma Qianquan , Nicholas Van Halm-Lutterodt , Sun Jianjun , Zhao Xiaofang , Liu Weihai , Yang Chenlong
Published: May 2023

Background

Paraganglioma in the sellar region is an extremely rare entity, with a limited number of cases reported in the literature. Due to the paucity of clinical evidence, the diagnosis and treatment of paragangliomas in the sellar region remain challenging. Herein, we reported a case of sellar paraganglioma with parasellar and suprasellar extension. Particularly, the dynamic evolution of this benign tumor within a 7-year longitudinal observation was presented. Additionally, the relevant literature regarding sellar paraganglioma was comprehensively reviewed.

Case description

A 70-year-old woman presented with progressive visual deterioration and headache. Brain magnetic resonance imaging demonstrated a mass in the sellar region with parasellar and suprasellar extension. The patient refused surgical treatment. Seven years later, brain magnetic resonance imaging showed the lesion significantly progressed. Neurological examination revealed bilateral tubular contraction of visual fields. Laboratory examinations showed endocrine hormone levels were normal. Surgical decompression was performed via a subfrontal approach, and subtotal resection was achieved. Histopathological examination confirmed a diagnosis of paraganglioma. Postoperatively, she developed hydrocephalus, and ventriculoperitoneal shunting was performed. Eight months later, cranial CT showed no recurrence of the residual tumor, and the hydrocephalus had been relieved.

Conclusion

Paraganglioma occurring in the sellar region is rare, and the preoperative differential diagnosis is difficult. Owing to the infiltration to the cavernous sinus and internal carotid, complete surgical resection is usually impracticable. There has been no consensus regarding postoperative adjuvant radiochemotherapy for the tumor residue. In-situ recurrence and metastasis have been reported in the literature, and close follow-up is warranted.
Patient characteristics and clinical factors affecting lumpectomy cavity volume: implications for partial breast irradiation
Authors: Le Amy , Achiko Flora Amy , Boyd LaKeisha , Shan Mu , Zellars Richard C. , Rhome Ryan M.
Published: May 2023

Introduction

Partial breast irradiation (PBI) has increased in utilization, with the postoperative lumpectomy cavity and clips used to guide target volumes. The ideal timing to perform computed tomography (CT)–based treatment planning for this technique is unclear. Prior studies have examined change in volume over time from surgery but not the effect of patient characteristics on lumpectomy cavity volume. We sought to investigate patient and clinical factors that may contribute to larger postsurgical lumpectomy cavities and therefore predict for larger PBI volumes.

Methods

A total of 351 consecutive women with invasive or in situ breast cancer underwent planning CT after breast-conserving surgery at a single institution during 2019 and 2020. Lumpectomy cavities were contoured, and volume was retrospectively computed using the treatment planning system. Univariate and multivariate analyses were performed to evaluate the associations between lumpectomy cavity volume and patient and clinical factors.

Results

Median age was 61.0 years (range, 30–91), 23.9% of patients were Black people, 52.1% had hypertension, the median body mass index (BMI) was 30.4 kg/m², 11.4% received neoadjuvant chemotherapy, 32.5% were treated prone, mean interval from surgery to CT simulation was 54.1 days ± 45.9, and mean lumpectomy cavity volume was 42.2 cm3 ± 52.0. Longer interval from surgery was significantly associated with smaller lumpectomy cavity volume on univariate analysis, p = 0.048. Race, hypertension, BMI, the receipt of neoadjuvant chemotherapy, and prone position remained significant on multivariate analysis (p < 0.05 for all). Prone position vs. supine, higher BMI, the receipt of neoadjuvant chemotherapy, the presence of hypertension, and race (Black people vs. White people) were associated with larger mean lumpectomy cavity volume.

Discussion

These data may be used to select patients for which longer time to simulation may result in smaller lumpectomy cavity volumes and therefore smaller PBI target volumes. Racial disparity in cavity size is not explained by known confounders and may reflect unmeasured systemic determinants of health. Larger datasets and prospective evaluation would be ideal to confirm these hypotheses.
Risks of prostate cancer and mortality in the city of Sharjah, United Arab Emirates
Authors: Al Shareef Zainab , Al-Shahrabi Rula , Saheb Sharif-Askari Fatemeh , Alshamsi Younis , Zarooni Abdulqadir Al , AlKhayyal Noura , Soliman Sameh S. M. , Bendardaf Riyad , Halwani Rabih
Published: May 2023

Background

Prostatic hyperplasia (BPH) and prostate cancer (PCa) are common age-related diseases in men. According to World Health Organization (WHO), PCa is the second most common cancer among Emirati men. This study aimed to identify the risk factors associated with PCa and mortality in a cohort diagnosed with PCa between 2012 and 2021 in Sharjah, United Arab Emirates (UAE).

Methods

The data collected in this retrospective case-control study included patient demographics and comorbidities, as well as PCa markers such as prostate-specific antigen (PSA), prostate volume, prostate-specific antigen density (PSAD), and Gleason scores. Risk factors for PCa were assessed using multivariate logistic regression analysis, and factors associated with all-cause mortality in PCa patients were evaluated using Cox-proportional hazard analysis.

Results

Of the 192 cases analyzed in this study, 88 were diagnosed with PCa and 104 were diagnosed with BPH. Regarding risk factors for PCa, a higher risk of PCa was associated with age 65 or older (OR=2.76, 95% confidence interval (CI): 1.04-7.30; P=0.038) and serum PSAD greater than 0.1 ng/mL2 (OR=3.48, 95% CI:1.66-7.32; P=0.001), whereas being of UAE nationals (OR=0.40, 95% CI:0.18-0.88; P=0.029) were associated with lower risk of PCa, after adjusting for patient demographics and comorbidities. Moreover, regarding cancer markers, higher serum PSA level (P=0.003) and smaller prostate volume (P=0.028) were associated with a higher risk of PCa, after adjusting with patients’ age and BMI. Additionally, a high-grade Gleason score was associated with an increased risk of all-cause mortality after adjusting for patient’s age and BMI (hazard ratio, aHR= 2.3, 95% CI:1.3-4.1; P= 0.016).

Conclusion

This study found that age 65 or older and serum PSAD greater than 0.1 ng/mL2 are risk factors for PCa, while UAE nationality is associated with a lower risk. PSAD may be a better screening marker for PCa compared to traditional markers such as PSA and prostate volume.
Safety, tolerability, pharmacokinetics, and immunogenicity of an anti-SARS-CoV-2 monoclonal antibody HFB30132A after single dose intravenous administration in healthy Chinese subjects: a phase 1, randomized, double-blind, placebo-controlled study
Authors: Li Shanshan , Wu Xiaojie , Li Nanyang , Cao Guoying , Wang Jingjing , Chen Yuancheng , Li Size , He Jinjie , Wu Jufang , Yang Haijing , Lin Ke , Qiu Chao , Liu Angela , Zhou He , Adrian Francisco , Schweizer Liang , Zhang Wenhong , Gu Jingwen , Zhang Jing
Published: May 2023

Objective: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) still protracts worldwide. HFB30132A is an anti- SARS-CoV-2 monoclonal antibody purposely engineered for an extended half-life with neutralizing activity against majority of the virus variants identified so far. The aim of this study was to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of HFB30132A in healthy Chinese subjects.

Methods: A phase 1, randomized, double-blind, placebo-controlled, single ascending dose clinical trial was designed. Twenty subjects were enrolled to Cohort 1 (1,000 mg dose level, 10 subjects) or Cohort 2 (2,000 mg dose level, 10 subjects). Subjects in each cohort were assigned randomly to receive a single intravenous (IV) dose of HFB30132A or placebo at a ratio of 8:2. Safety was assessed in terms of treatment emergent adverse events (TEAEs), vital signs, physical examination, laboratory tests, and ECG findings. PK parameters were measured and calculated appropriately. Anti-drug antibody (ADA) test was performed to detect anti-HFB30132A antibodies.

Results: All subjects completed the study. Overall, 13 (65%) of the 20 subjects experienced TEAEs. The most common TEAEs were laboratory abnormalities (12 subjects [60%]), gastrointestinal disorders (6 subjects [30%]), and dizziness (4 subjects [20%]). All TEAEs were Grade 1 or Grade 2 in severity based on the criteria of Common Terminology Criteria for Adverse Events (CTCAE). Serum exposure (Cmax, AUC0-t, AUC0-∞) of HFB30132A increased with ascending dose. After single dose of 1,000 mg and 2000 mg HFB30132A, the mean Cmax was 570.18 μg/mL and 898.65 μg/mL, the mean AUC0-t value was 644,749.42 h*μg/mL and 1,046,209.06 h*μg/mL, and the mean AUC0-∞ value was 806,127.47 h*μg/mL and 1,299,190.74 h*μg/mL, respectively. HFB30132A showed low clearance ranging from 1.38 to 1.59 mL/h, and a long terminal elimination half-life (t½) of 89–107 days. ADA test did not detect any anti-HFB30132A antibodies

Conclusion: HFB30132A was safe and generally well-tolerated after single IV dose of 1,000 mg or 2000 mg in healthy Chinese adults. HFB30132A did not induce immunogenic response in this study. Our data support further clinical development of HFB30132A.

Clinical Trial Registration:https://clinicaltrials.gov, identifier: NCT05275660.
A comprehensive review of acute cardio-renal syndrome: need for novel biomarkers
Authors: Dutta Abhi , Saha Shubham , Bahl Ajay , Mittal Anupam , Basak Trayambak
Published: May 2023

Cardiorenal syndrome represents a wide-spectrum disorder involving the heart and kidneys as the primary affected organs. India has an increasingly high burden of acute CRS, coinciding with the rise in global statistics. Up to 2022, approximately 46.1% of all cardiorenal patients have been diagnosed with acute CRS in India. Acute CRS involves a sudden deterioration of kidney functionalities, referred to as acute kidney injury (AKI) in acute heart failure patients. The pathophysiology of CRS involves hyperactivation of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS) following acute myocardial stress. The pathological phenotype of acute CRS is associated with perturbed inflammatory, cellular, and neurohormonal markers in circulation. These complications increase the risk of mortality in clinically diagnosed acute CRS patients, making it a worldwide healthcare burden. Hence, effective diagnosis and early prevention are crucial to prevent the progression of CRS in AHF patients. Present biomarkers, such as serum creatinine (sCr), cystatin C (CysC), glomerular filtration rate (GFR), blood urea nitrogen (BUN), serum and/or urine neutrophil gelatinase-associated lipocalin (NGAL), B-type natriuretic peptide (BNP), and NT-proBNP, are clinically used to diagnose AKI stages in CRS patients but are limitedly sensitive to the early detection of the pathology. Therefore, the need for protein biomarkers is emerging for early intervention in CRS progression. Here, we summarized the cardio-renal nexus in acute CRS, with an emphasis on the present clinicopathological biomarkers and their limitations. The objective of this review is to highlight the need for novel proteomic biomarkers that will curb the burgeoning concern and direct future research trials.
Detection of potential drug-drug interactions for risk of acute kidney injury: a population-based case-control study using interpretable machine-learning models
Authors: Akimoto Hayato , Hayakawa Takashi , Nagashima Takuya , Minagawa Kimino , Takahashi Yasuo , Asai Satoshi
Published: May 2023

Background: Acute kidney injury (AKI), with an increase in serum creatinine, is a common adverse drug event. Although various clinical studies have investigated whether a combination of two nephrotoxic drugs has an increased risk of AKI using traditional statistical models such as multivariable logistic regression (MLR), the evaluation metrics have not been evaluated despite the fact that traditional statistical models may over-fit the data. The aim of the present study was to detect drug-drug interactions with an increased risk of AKI by interpreting machine-learning models to avoid overfitting.

Methods: We developed six machine-learning models trained using electronic medical records: MLR, logistic least absolute shrinkage and selection operator regression (LLR), random forest, extreme gradient boosting (XGB) tree, and two support vector machine models (kernel = linear function and radial basis function). In order to detect drug-drug interactions, the XGB and LLR models that showed good predictive performance were interpreted by SHapley Additive exPlanations (SHAP) and relative excess risk due to interaction (RERI), respectively.

Results: Among approximately 2.5 million patients, 65,667 patients were extracted from the electronic medical records, and assigned to case (N = 5,319) and control (N = 60,348) groups. In the XGB model, a combination of loop diuretic and histamine H2 blocker [mean (|SHAP|) = 0.011] was identified as a relatively important risk factor for AKI. The combination of loop diuretic and H2 blocker showed a significant synergistic interaction on an additive scale (RERI 1.289, 95% confidence interval 0.226–5.591) also in the LLR model.

Conclusion: The present population-based case-control study using interpretable machine-learning models suggested that although the relative importance of the individual and combined effects of loop diuretics and H2 blockers is lower than that of well-known risk factors such as older age and sex, concomitant use of a loop diuretic and histamine H2 blocker is associated with increased risk of AKI.
Genotype-by-environment interactions for starch, mineral, and agronomic traits in pearl millet hybrids evaluated across five locations in West Africa
Authors: Gangashetty Prakash I. , Yadav Chandra Bhan , Riyazaddin Mohammed , Vermula Anilkumar , Asungre Peter Anabire , Angarawai Ignatitius , Mur Luis A. J. , Yadav Rattan S.
Published: May 2023

Introduction

Pearl millet is a staple cereal grown in the harshest environments of arid and semi-arid regions of Asia and sub-Saharan Africa. It is the primary source of calories for millions of people in these regions because it has better adaptation to harsh environmental conditions and better nutritional traits than many other cereals. By screening the pearl millet inbred germplasm association panel (PMiGAP), we earlier reported the best genotypes with the highest concentration of slowly digestible and resistant starch in their grains.

Methods

In the current study, we tested these 20 top-performing pearl millet hybrids, identified based on starch data, in a randomised block design with three replications at five locations in West Africa, viz. Sadore and Konni (Niger), Bambey (Senegal), Kano (Nigeria), and Bawku (Ghana). Phenotypic variability was assessed for agronomic traits and mineral traits (Fe and Zn).

Results and discussion

Analysis of variance demonstrated significant genotypic, environmental, and GEI effects among five testing environments for agronomic traits (days to 50% flowering, panicle length, and grain yield), starch traits (rapidly digestible starch, slowly digestible starch, resistant starch, and total starch), and mineral trait (iron and zinc). Starch traits, such as rapidly digestible starch (RDS) and slowly digestible starch (SDS), showed nonsignificant genotypic and environmental interactions but high heritability, indicating the lower environmental influence on these traits in the genotype × testing environments. Genotype stability and mean performance across all the traits were estimated by calculating the multi-trait stability index (MTSI), which showed that genotypes G3 (ICMX207070), G8 (ICMX207160), and G13 (ICMX207184) were the best performing and most stable among the five test environments.
Understanding the interplay between text quality, writing self-efficacy and writing anxiety in learners with and without migration background
Authors: Busse Vera , Graham Steve , Müller Nora , Utesch Till
Published: May 2023

Writing presents considerable challenges to students’ motivation. Yet there is a dearth of studies assessing the role of affect and motivation in writing performance for students with migration backgrounds (MB), who often underachieve in writing. Our study addressed this research gap by investigating the interplay between writing self-efficacy, writing anxiety, and text quality in 208 secondary students with and without MB using Response Surface Analyses. The data showed comparable levels of self-efficacy and, notably, lower writing anxiety levels among students with MB despite lower writing achievements. In the full sample, we observed positive correlations between self-efficacy and text quality and negative correlations between writing anxiety and text quality. When modeling efficacy and anxiety measures and their interplay to predict text quality, self-efficacy measures continued to account for statistically detectable unique variance in text quality, whereas writing anxiety did not. However, students with MB demonstrated differing interplay patterns, with less efficacious students with MB showing positive relations between writing anxiety and text quality.
Exploring the nature of the gender-congruency effect: implicit gender activation and social bias
Authors: Casado Alba , Sá-Leite Ana Rita , Pesciarelli Francesca , Paolieri Daniela
Published: May 2023

The aim of the study was to explore the nature of the gender-congruency effect, characterized by a facilitation on the processing of congruent words in grammatical gender. Moreover, we explored whether resemblances between gender identities and gender attitudes with grammatical gender modulated lexical processing. We designed a gender-priming paradigm in Spanish, in which participants decided the gender of a masculine or feminine pronoun preceded by three different primes: biological gender nouns (mapping biological sex), stereotypical nouns (mapping biological and stereotypical information), and epicene nouns (arbitrary gender assignment). We found faster processing of gender congruent pronouns independently of the type of prime, showing that the grammatical gender feature is active even when processing bare nouns that are not conceptually related to gender. This indicates that the gender-congruency effect is driven by the activation of the gender information at the lexical level, which is transferred to the semantic level. Interestingly, the results showed an asymmetry for epicene primes: the gender-congruency effect was smaller for epicene primes when preceding the feminine pronoun, probably driven by the grammatical rule of the masculine being the generic gender. Furthermore, we found that masculine oriented attitudes can bias language processing diminishing the activation of feminine gender, which ultimately could overshadow the female figure.
Should I post? The relationships among social media use, emotion recognition, and mental health
Authors: Scarpulla Emily , Stosic Morgan D. , Weaver Adele E. , Ruben Mollie A.
Published: May 2023

Introduction

While increased time spent on social media can be negatively related to one’s overall mental health, social media research often fails to account for what behaviors users are actually engaging in while they are online. The present research helps to address this gap by measuring participants’ active and passive social media behavioral styles and investigates whether and how these two social media behavioral styles are related to depression, anxiety, and stress, and the mediating role of emotion recognition ability in this relationship.

Methods

A pre-study (N = 128) tested whether various social media behaviors reliably grouped into active and passive behavioral styles, and a main study (N = 139) tested the relationships between social media use style, emotion recognition, and mental health.

Results

While we did not find evidence of a mediating relationship between these variables, results supported that more active social media use was related to more severe anxiety and stress as well as poorer emotion recognition skill, while passive social media use was unrelated to these outcomes.

Discussion

These findings highlight that, beyond objective time spent on social media, future research must consider how users are spending their time online.
The effect of working memory updating training on the Chinese writing ability of primary school students
Authors: Gao Jiacheng , Li Guangxin , Yang Zimo , Li Fengjuan , Wang Tian , Wen Suxia
Published: May 2023

Objective

This study aimed to explore the effects of working memory updating training on primary school students' writing ability and performance.

Methods

A total of 46 fourth-grade Chinese primary school students were recruited; their performance in the Chinese character N-back training task, the Writing Ability Questionnaire, and a time-limited writing task was assessed.

Results

The paired-sample t-test revealed that working memory updating training significantly improved the experimental group's working memory level. After training, a repeated measures ANOVA revealed that the experimental group's performance on the Writing Ability Questionnaire improved and was higher than that of the control group. In the time-limited writing task, independent-sample t-tests revealed that the experimental group's writing fluency increased and was higher than that of the control group, while the latter's grammatical accuracy and complexity decreased and were lower than those of the former.

Conclusion

Working memory updating training can be used as auxiliary cognitive training to improve primary school students' working memory level, thereby promoting their writing development.