bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors associated with high placebo response in clinical studies of hot flashes: a meta-analysis
Authors: Miyazaki Kentaro , Kaneko Masayuki , Narukawa Mamoru 
Published: November 2021

Abstract

Importance:
High placebo response can often mask the evaluation of active treatment in clinical studies for women with hot flashes and potentially undermine the evaluation of new treatments.

Objective:
The aim of this meta-analysis was to determine the factors associated with high placebo response (defined as the reduction in the mean number of hot flash frequency from baseline) in randomized, controlled, double-blind studies enrolling women with hot flashes.

Evidence Review:
To identify eligible studies, Embase, MEDLINE, and BIOSIS Previews were searched for English-language articles published between April 1975 and August 2020. Placebo-controlled, double-blind, randomized studies that assessed changes in hot flash frequency were included if they satisfied the defined criteria. We conducted univariate and multivariate analyses using categorical and numerical data. Categorical data included the following variables and levels in brackets: active treatment type (hormone therapy /non- hormone therapy /complementary and alternative medicine), administration route (oral/non-oral), study region (in/excluded the US), breast cancer population (in/excluded), entry criteria of hot flash severity (moderate to severe only/all included), parallel or crossover study, placebo run-in period before treatment (yes/no), and menopausal status (postmenopausal only/include perimenopausal/include premenopausal). Numerical data included published year, pretreatment period duration, treatment period duration, number of sites, number of total participants, number of placebo participants, number of treatment arms, mean age, BMI, and hot flash frequency at baseline.

Findings:
Forty-three of the 802 identified publications were included in the review. Multivariate analysis identified three individual factors associated with high placebo response: treatment period duration, number of treatment arms, and BMI.

Conclusions and Relevance:
We identified several factors associated with high placebo response in clinical studies of women with hot flashes. Knowing these factors may enable proactive implementation of operational and analytic strategies that further aid in determining the true treatment effect of an intervention.
Opioid-sparing Strategies in Alloplastic Breast Reconstruction: A Systematic Review
Authors: Crystal Dustin T. , Ibrahim Ahmed M. S. , Blankensteijn Louise L. , Cuccolo Nicholas G. , Kazei Darya , Zitkovsky Helen S. , Lee Bernard T. , Lin Samuel J. 
Published: November 2021

Introduction:
Pain and discomfort are frequently experienced following mastectomy with concomitant breast implant- or tissue expander-based alloplastic breast reconstruction (AlBR). Unfortunately, postoperative opioids have decreased efficacy in AlBR, short-term complication profiles, and are fraught by long-term dependence. This systematic review aims to identify opioid-sparing pain management strategies in AlBR.

Methods:
A systematic literature search of MEDLINE, Embase, Web of Science, and Cochrane Central Register was performed in September 2018. PRISMA guidelines were followed, and the review was prospectively registered in PROSPERO (CRD42018107911). The search identified 1184 articles. Inclusion criteria were defined as patients 18 years or older undergoing AlBR.

Results:
Fourteen articles were identified assessing opioid-sparing strategies in AlBR. This literature included articles evaluating enhanced recovery protocols (two), intercostal blocks (two), paravertebral blocks (four), liposomal bupivacaine (three), diclofenac (one), and local anesthesia infusion pumps (two). The literature included five randomized trials and nine cohort studies. Study characteristics, bias (low to high risk), and reporting outcomes were extensively heterogeneous between articles. Qualitative analysis suggests reduced opioid utilization in enhanced recovery after surgery (ERAS) pathways, paravertebral blocks, and use of liposomal bupivacaine.

Conclusions:
A variety of opioid-sparing strategies are described for pain management in AlBR. Multimodal analgesia should be provided via ERAS pathways as they appear to reduce pain and spare opioid use. Targeted paravertebral blocks and liposomal bupivacaine field blocks appear to be beneficial in sparing opioids and should be considered as essential components of ERAS protocols. Additional prospective, randomized trials are necessary to delineate the efficacy of other studied modalities.
Loose zonules in cataract surgery
Authors: Venkateswaran Nandini , Henderson Bonnie A. 
Published: November 2021

Purpose of review
This review will focus on identifying causes of zonulopathy during cataract surgery and discuss various modalities for treatment.

Recent findings
There are multiple different options for capsular bag support in the setting of zonulopathy, including capsular or iris hooks, capsular tension rings as well as capsular tension segments (CTS). Surgical techniques on how to insert these devices are many and can be customized based upon the surgeon's preference and the patient's eye anatomy.

Summary
Recognizing zonular weakness is critical to achieve stable postoperative vision and avoid future complications. Depending on the degree of zonulopathy, various treatment options can be pursued, ranging from capsular tension hooks or iris hooks, capsular tension rings or sutured or scleral fixated CTS.
Reference values of mandibular condylar growth activity: a study of SUVmax with quantitative bone SPECT/CT
Authors: Lin Zefang , Xue Qianqian , Lin Rong , Yao Shaobo , Miao Weibing 
Published: November 2021

Objective
To assess the condylar growth activity (CGA) with quantitative bone single photon emission computed tomography/computed tomography (SPECT/CT) to establish reference values of maximum standardized uptake value (SUVmax) and cutoff values for identifying active unilateral condylar hyperplasia (UCH) in different ages.

Methods
We analyzed the CGA of 58 UCH patients and that of 125 volunteers as a control group by SUVmax of quantitative bone SPECT/CT imaging. The SUVmax and the uptake difference between bilateral condyles among different age groups were analyzed. SUVmax cutoff values for detecting active condyle were calculated by receiver operating characteristic curve analysis.

Results
The condylar SUVmax in 10–19, 20–29, 30–39, 40–49 and 50–59 years old groups of volunteers were 6.24 ± 1.39, 4.76 ± 0.98, 3.23 ± 0.64, 3.00 ± 0.61 and 2.90 ± 0.53, respectively. The uptake difference between bilateral condyles in the control group was 3.84% ± 1.71%. The affected condylar SUVmax was significantly higher than that of the contralateral condyle in active UCH patients (6.03 ± 2.85 vs. 3.96 ± 1.07; Z = −5.264; P = 0.000). SUVmax of the affected condyles in active UCH patients was not statistically higher than condylar SUVmax in the corresponding age group (6.03 ± 2.85 vs. 5.50 ± 1.41; Z = −0.173; P = 0.863). SUVmax of the unaffected condyles was significantly lower than condylar SUVmax in the corresponding age group (3.96 ± 1.07 vs. 5.50 ± 1.41; Z = −5.833; P = 0.000). SUVmax cutoff values for identifying active condyle were 6.26 and 4.53 in patients of 13–19 and 20–29 years old, respectively.

Conclusions
The condylar SUVmax varied with age. Different cutoff values of condylar SUVmax should be employed for diagnosing active UCH for patients in different ages.
The impact of 18F-fluorodeoxyglucose PET/computed tomography on clinical staging in bladder cancer
Authors: Coskun Nazim , Cagdas Berkay , Eroglu Unsal , Aslan Yilmaz , Turkolmez Seyda 
Published: November 2021

Aim
To determine the impact of 18F-FDG PET/computed tomography (CT) on clinical staging in bladder cancer with comparison to conventional CT and MRI.

Methods
A total of 142 patients who underwent 18F-FDG PET/CT imaging with a diagnosis of bladder cancer between 1 June 2019 and 31 December 2020 were screened retrospectively. Seventy patients who underwent diagnostic CT or MRI within 2 months before or after PET/CT were included in the study. The N and M stages determined by CT, MRI and PET/CT according to the eighth version of the TNM staging system were recorded. T-test was used to determine the levels of significant difference, and univariate logistic regression analysis was used to evaluate the impact of the T stage on nodal up-staging.

Results
According to the PET/CT, the N stage increased in 19 patients (27.14%) and decreased in seven patients (10%). Likewise, the M stage increased in 16 patients (22.86%) and decreased in seven patients (10%). The N stage determined by PET/CT was confirmed by pathologic examination in all cases in which the two modalities were inconsistent. In muscle-invasive cases, the rate of increase in the N stage after PET/CT (36.95%) was found to be significantly higher than in that of cases without invasion (8.33%) (P = 0.011). Increasing T stage was associated with an increase in the N stage after PET/CT (odds ratio: 2.33, 95% confidence interval: 1.02–5.28, P = 0.042).

Conclusion

18F-FDG PET/CT can potentially change the clinical stage determined by CT and MRI when used for staging in bladder cancer, and can lead to nodal up-staging particularly in cases with muscle-invasive bladder cancer.
Von Hippel–Lindau disease-associated renal cell carcinoma: a call to action
Authors: Larcher Alessandro , Rowe Isaline , Belladelli Federico , Fallara Giuseppe , Raggi Daniele , Necchi Andrea , Montorsi Francesco , Capitanio Umberto , Salonia Andrea 
Published: November 2021

Purpose of review
While the molecular and genetic bases of Von Hippel–Lindau (VHL) disease have been extensively investigated, limited evidence is available to guide diagnosis, local or systemic therapy, and follow-up. The aim of the current review is to summarize the ongoing trials both in preclinical and clinical setting regarding VHL disease management.

Recent findings
Although genotype/phenotype correlations have been described, there is considerable inter and intra-familiar heterogeneity in VHL disease. Genetic anticipation has been reported in VHL disease. From a clinical point of view, expert-opinion-based protocols suggest testing those patients with any blood relative of an individual diagnosed with VHL disease, those with at least 1 or more suggestive neoplasms or patients presenting with clear cell renal cell carcinoma (ccRCC) diagnosed at a less than 40 years old, and/or multiple ccRCC. Clinical research is focused on safety and efficacy of systemic agents for patients with VHL-related ccRCC, with the aim to possibly preserve kidney function and improve patient survival.

Summary
To date, preclinical and clinical research on the topic is scarce and clinical guidelines are not supported by strong validation studies.
Development of an accessible gene expression bioinformatics pipeline to study driver mutations of colorectal cancer
Authors: van den Driest Lisa , Johnson Caroline H , Rattray Nicholas JW , Rattray Zahra 
Published: November 2021

AbstractColorectal cancer (CRC) is a global cause of cancer-related mortality driven by genetic and environmental factors which influence therapeutic outcomes. The emergence of next-generation sequencing technologies enables the rapid and extensive collection and curation of genetic data for each cancer type into clinical gene expression biobanks.In this study we used a combination of bioinformatics tools to investigate the expression patterns and prognostic significance of two genes, adenomatous polyposis coli (APC) and B-Raf proto-oncogene (BRAF), that are commonly dysregulated in colon cancer. Subsequently, we investigated the pathways and biomolecular effectors implicated in APC and BRAF function.Our results show mutation types, frequency, anatomical location and differential expression patterns for APC and BRAF between colorectal tumour and matched healthy tissue. The prognostic values of APC and BRAF was investigated as a function of expression level in CRC and other cancer types.In the era of precision medicine and with significant advancements in biobanking and data curation, there is significant scope to use existing clinical datasets for evaluating the role of mutational drivers in carcinogenesis. This offers the potential for studying combinations of less well-known genes and the discovery of novel biomarkers or studying the association between various effector proteins and pathways.
Rewiring glucose metabolism improves 5-FU efficacy in glycolytic p53-deficient colorectal tumors
Authors: Ludikhuize Marlies C. , Gevers Sira , Nguyen Nguyen T.B. , Meerlo Maaike , Shafiei Roudbari S. Khadijeh , Gulersonmez M. Can , Stigter Edwin C.A. , Drost Jarno , Clevers Hans , Burgering Boudewijn M.T. , Rodríguez Colman Maria J. 
Published: November 2021

Abstract5-fluorouracil (5-FU) is the backbone for chemotherapy in colorectal cancer (CRC). Response rates in patients are, however, limited to 50%. Despite the importance of 5-FU, the molecular mechanisms by which it induces toxicity remain unclear, limiting the development of strategies to improve efficacy. How fundamental aspects of cancer, such as driver mutations and phenotypic intra-tumor heterogeneity, relate to the 5-FU response is also ill-defined. This is largely due to the shortage of mechanistic studies executed in pre-clinical models that can faithfully recapitulate key CRC features. Here, we analyzed the 5-FU response in human organoids genetically engineered to reproduce the different stages of CRC progression. We find that 5-FU induces pyrimidine imbalance, which leads to DNA damage and cell death. Actively proliferating cancer (stem) cells are accordingly efficiently targeted by 5-FU. Importantly, p53 behaves as a discriminating factor for 5-FU sensitivity, whereas p53-deficiency leads to DNA damage-induced cell death, active p53 protects from these effects through inducing cell cycle arrest. Moreover, we find that targeting the Warburg effect, by rewiring glucose metabolism, enhances 5-FU toxicity by further altering the nucleotide pool and without increasing toxicity in healthy-non-transformed cells. Thus, targeting cancer metabolism in combination with replication stress-inducing chemotherapies emerges as a promising strategy for CRC treatment.
The Genomic Prehistory of the Indigenous People of Uruguay
Authors: Lindo John , De La Rosa Rosseirys , dos Santos Andre Luiz Campelo , Sans Mónica , DeGiorgio Michael , Figueiro Gonzalo 
Published: November 2021

AbstractThe prehistory of the people of Uruguay is greatly complicated by the dramatic and severe effects of European contact, as with most of the Americas. After the series of military campaigns that exterminated the last remnants of nomadic peoples, Uruguayan official history masked and diluted the former indigenous ethnic diversity into the narrative of a singular people that all but died out. Here we present the first whole genome sequences of the Indigenous people of the region before the arrival of Europeans, from an archaeological site in eastern Uruguay that dates from 2,000 years before present. We find a surprising connection to ancient individuals from Panama and eastern Brazil, but not to modern Amazonians. This result may be indicative of a distinct migration route into South America that may have occurred along the Atlantic coast. We also find a distinct ancestry previously undetected in South America. Though this work begins to piece together some of the demographic nuance of the region, the sequencing of ancient individuals from across Uruguay is needed to better understand the ancient prehistory and genetic diversity that existed before European contact, thereby helping to rebuild the history of the indigenous population of what is now Uruguay.
CAN A MACHINE LEARNING ALGORITHM IDENTIFY SARS-COV-2 VARIANTS BASED ON CONVENTIONAL rRT-PCR? PROOF OF CONCEPT
Authors: Cabrera Alvargonzález Jorge , Larrañaga Janeiro Ana , Pérez Castro Sonia , Martínez Torres Javier , Martínez Lamas Lucía , Daviña Nuñez Carlos , Del Campo-Pérez Víctor , Suarez Luque Silvia , García Benito Regueiro , Porteiro Fresco Jacobo 
Published: November 2021

1ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been and remains one of the major challenges humanity has faced thus far. Over the past few months, large amounts of information have been collected that are only now beginning to be assimilated. In the present work, the existence of residual information in the massive numbers of rRT-PCRs that tested positive out of the almost half a million tests that were performed during the pandemic is investigated. This residual information is believed to be highly related to a pattern in the number of cycles that are necessary to detect positive samples as such. Thus, a database of more than 20,000 positive samples was collected, and two supervised classification algorithms (a support vector machine and a neural network) were trained to temporally locate each sample based solely and exclusively on the number of cycles determined in the rRT-PCR of each individual. Finally, the results obtained from the classification show how the appearance of each wave is coincident with the surge of each of the variants present in the region of Galicia (Spain) during the development of the SARS-CoV-2 pandemic and clearly identified with the classification algorithm.
The manipulation of spinal motor neuron axonal growth promotes spinal cord repair
Authors: Wang Feng , Fu Xin-Ya , Li Mei-Mei , Wang Xing-Ran , Xie Ji-Le , Ma Jin-Jin , Ma Yan-Xia , Saijilafu  
Published: November 2021

AbstractThe loss of motor function in patients with spinal cord injury (SCI) is primarily due to the severing of the corticospinal tract (CST). Spinal motor neurons are located in the anterior horn of the spinal cord, and as the lower neurons of the CST, they control voluntary movement. Furthermore, its intrinsic axonal growth ability is significantly stronger than that of cerebral cortex pyramid neurons, which are the upper CST neurons. Therefore, we established an axonal regeneration model of spinal motor neurons to investigate the feasibility of repairing SCI by promoting axonal regeneration of spinal motor neurons. We demonstrated that conditionally knocking out pten in mature spinal motor neurons drastically enhanced axonal regeneration in vivo, and the regenerating axons of the spinal motor neurons re-established synapses with other cells in the damaged spinal cord. Thus, this strategy may serve as a novel and effective treatment method for SCI.
A live attenuated influenza virus-vectored intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2 infection
Authors: Chen Junyu , Wang Pui , Yuan Lunzhi , Zhang Liang , Zhang Limin , Zhao Hui , Chen Congjie , Chen Yaode , Han Jinle , Jia Jizong , Lu Zhen , Hong Junping , Chen Liqiang , Fan Changfa , Lu Zicen , Wang Qian , Chen Rirong , Cai Minping , Qi Ruoyao , Wang Xijing , Ma Jian , Zhou Min , Yu Huan , Zhuang Chunlan , Liu Xiaohui , Han Qiangyuan , Wang Guosong , Su Yingying , Yuan Quan , Cheng Tong , Wu Ting , Ye Xiangzhong , Li Changgui , Zhang Tianying , Zhang Jun , Zhu Huachen , Chen Yixin , Chen Honglin , Xia Ningshao 
Published: November 2021

AbstractRemarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 day and 7 days after single-dose vaccination or 6 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight, caused by either the prototype-like strain or beta variant of SARS-CoV-2. Lasted data showed that the animals could be well protected against beta variant challenge 9 months after vaccination. Notably, the weight loss and lung pathological changes of hamsters could still be significantly reduced when the hamster was vaccinated 24 h after challenge. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to fight against the ongoing COVID-19 pandemic, compensating limitations of current intramuscular vaccines, particularly at the start of an outbreak.
A computational study on the optimization of transcranial temporal interfering stimulation with high-definition electrode using unsupervised neural network
Authors: Bahn Sang-kyu , Kang Bo-Yeong , Lee Chany 
Published: November 2021

ABSTRACTTranscranial temporal interfering stimulation (tTIS) can focally stimulate deep parts of the brain, which are related to specific functions, by using beats at two high AC frequencies that do not affect the human brain. However, it has limitations in terms of calculation time and precision for optimization because of its complexity and non-linearity. We aimed to propose a method using an unsupervised neural network (USNN) for tTIS to optimize quickly the interfering current value of high-definition electrodes, which can finely stimulate the deep part of the brain, and analyze the performance and characteristics of tTIS. A computational study was conducted using 16 realistic head models. This method generated the strongest stimulation on the target, even when targeting deep areas or multi-target stimulation. The tTIS was robust with target depth compared with transcranial alternating current stimulation, and mis-stimulation could be reduced compared with the case of using two-pair inferential stimulation. Optimization of a target could be performed in 3 min. By proposing the USNN for tTIS, we showed that the electrode currents of tTIS can be optimized quickly and accurately, and the possibility of stimulating the deep part of the brain precisely with transcranial electrical stimulation was confirmed.
Assessment of Airborne Disease Transmission Risk and Energy Impact of HVAC Mitigation Strategies
Authors: Risbeck Michael J. , Bazant Martin Z. , Jiang Zhanhong , Lee Young M. , Drees Kirk H. , Douglas Jonathan D. 
Published: November 2021

AbstractThe COVID-19 pandemic has focused renewed attention on the ways in which building HVAC systems may be operated to mitigate the risk of airborne disease transmission. The most common suggestion is to increase outdoor-air ventilation rates so as to dilute the concentrations of infectious aerosol particles indoors. Although this strategy does reduce the likelihood of disease spread, it is often much more costly than other strategies that provide equivalent particle removal or deactivation. To address this tradeoff and arrive at practical recommendations, we explain how different mitigation strategies can be expressed in terms of equivalent outdoor air (EOA) to provide a common basis for energy analysis. We then show the effects of each strategy on EOA delivery and energy cost in simulations of realistic buildings in a variety of climates. Key findings are that in-duct filtration is often the most efficient mitigation strategy, while significant risk reduction generally requires increasing total airflow to the system, either through adjusted HVAC setpoints or standalone disinfection devices.