bluuebunny/crossref_metadata_2025 huggingface dataset:
KCNJ14 knockdown significantly inhibited the proliferation and migration of colorectal cells
Authors: Li Bin , Ge Ning , Pan Zhongping , Hou Chaofeng , Xie Kun , Wang Dongfang , Liu Junwei , Wan Jie , Deng Feihong , Li Mengyi , Luo Shuping
Published: September 2022

Background

This study attempted to verify the potential of KCNJ14 as a biomarker in colorectal cancer (CRC).

Methods

Data on transcriptomics and DNA methylation and the clinical information of CRC patients were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. Biological information analysis methods were conducted to determine the role of KCNJ14 in the prognosis, diagnosis, immune cell infiltration, and regulation mechanism of CRC patients. The effect of KCNJ14 on the proliferation and migration of HCT116 and SW480 CRC cell lines was verified by in vitro experiments (MTT, colony-forming, wound healing, and transwell assays). Western blotting was performed to detect the effect of KCNJ14 on the levels of mTOR signalling pathway-related proteins.

Results

KCNJ14 expression was remarkably increased in CRC tissues and cell lines, which reduced the overall survival time of patients. KCNJ14 mRNA was negatively regulated by its methylation site cg17660703, which can also endanger the prognosis of patients with CRC. Functional enrichment analysis suggested that KCNJ14 is involved in the mTOR, NOD-like receptor, and VEGF signalling pathways. KCNJ14 expression was positively correlated with the number of CD4 + T cells and negatively correlated with that of CD8 + T cells in the immune microenvironment. KCNJ14 knockdown significantly reduced not only the proliferation and migration of CRC cell lines but also the levels of mTOR signalling pathway-related proteins.

Conclusions

This study not only increases the molecular understanding of KCNJ14 but also provides a potentially valuable biological target for the treatment of colorectal cancer.
TRIM proteins in hepatocellular carcinoma
Authors: Lu Kan , Pan Yonglong , Huang Zhao , Liang Huifang , Ding Ze-yang , Zhang Bixiang
Published: September 2022

The tripartite motif (TRIM) protein family is a highly conserved group of E3 ligases with 77 members known in the human, most of which consist of a RING-finger domain, one or two B-box domains, and a coiled-coil domain. Generally, TRIM proteins function as E3 ligases to facilitate specific proteasomal degradation of target proteins. In addition, E3 ligase independent functions of TRIM protein were also reported. In hepatocellular carcinoma, expressions of TRIM proteins are both regulated by genetic and epigenetic mechanisms. TRIM proteins regulate multiple biological activities and signaling cascades. And TRIM proteins influence hallmarks of HCC. This review systematically demonstrates the versatile roles of TRIM proteins in HCC and helps us better understand the molecular mechanism of the development and progression of HCC.
An investigation of privacy preservation in deep learning-based eye-tracking
Authors: Seyedi Salman , Jiang Zifan , Levey Allan , Clifford Gari D.
Published: September 2022

Background

The expanding usage of complex machine learning methods such as deep learning has led to an explosion in human activity recognition, particularly applied to health. However, complex models which handle private and sometimes protected data, raise concerns about the potential leak of identifiable data. In this work, we focus on the case of a deep network model trained on images of individual faces.

Materials and methods

A previously published deep learning model, trained to estimate the gaze from full-face image sequences was stress tested for personal information leakage by a white box inference attack. Full-face video recordings taken from 493 individuals undergoing an eye-tracking- based evaluation of neurological function were used. Outputs, gradients, intermediate layer outputs, loss, and labels were used as inputs for a deep network with an added support vector machine emission layer to recognize membership in the training data.

Results

The inference attack method and associated mathematical analysis indicate that there is a low likelihood of unintended memorization of facial features in the deep learning model.

Conclusions

In this study, it is showed that the named model preserves the integrity of training data with reasonable confidence. The same process can be implemented in similar conditions for different models.
Mesenchymal stem cell-derived exosomes in cancer therapy resistance: recent advances and therapeutic potential
Authors: Lin Zhengjun , Wu Yanlin , Xu Yiting , Li Guoqing , Li Zhihong , Liu Tang
Published: September 2022

Mesenchymal stem cells (MSCs) are multipotent stromal cells that can be obtained from various human tissues and organs. They can differentiate into a wide range of cell types, including osteoblasts, adipocytes and chondrocytes, thus exhibiting great potential in regenerative medicine. Numerous studies have indicated that MSCs play critical roles in cancer biology. The crosstalk between tumour cells and MSCs has been found to regulate many tumour behaviours, such as proliferation, metastasis and epithelial-mesenchymal transition (EMT). Multiple lines of evidence have demonstrated that MSCs can secrete exosomes that can modulate the tumour microenvironment and play important roles in tumour development. Notably, very recent works have shown that mesenchymal stem cell-derived exosomes (MSC-derived exosomes) are critically involved in cancer resistance to chemotherapy agents, targeted-therapy drugs, radiotherapy and immunotherapy. In this review, we systematically summarized the emerging roles and detailed molecular mechanisms of MSC-derived exosomes in mediating cancer therapy resistance, thus providing novel insights into the clinical applications of MSC-derived exosomes in cancer management.
Associations of eating speed with fat distribution and body shape vary in different age groups and obesity status
Authors: Ni Saili , Jia Menghan , Wang Xuemiao , Hong Yun , Zhao Xueyin , Zhang Liang , Ru Yuan , Yang Fei , Zhu Shankuan
Published: September 2022

Background

Eating speed has been reported to be associated with energy intake, body weight, waist circumference (WC), and total body fat. However, no study has explored the association between eating speed and body fat distribution, especially its difference among different age or body mass index (BMI) groups.

Methods

4770 participants aged 18–80 years were recruited from the baseline survey of the Lanxi Cohort Study. They were categorized into three groups according to meal duration. Linear regression analyses were performed among all participants and separately by age group and obesity status to evaluate the associations of WC and total and regional fat mass percentages (FM%) with eating speed.

Results

After adjusting for confounding factors, eating slowly was significantly related to lower WC, lower total, trunk, and android FM%, lower android-to-gynoid fat mass ratio, and higher leg and gynoid FM%. After stratification by age or obesity status, the associations were especially prominent among participants aged 18–44 years or those with BMI < 24 kg/m2. No significant trends were found for participants aged 65–80 years or those who were overweight/obese.

Conclusions

Eating slowly is closely related with better fat distribution among Chinese adults, especially for those aged 18–44 years and those with BMI < 24 kg/m2. If confirmed prospectively, it might be a potential efficient approach to improve fat distribution.
The first reported case of a patient with pancreatic cancer treated with cone beam computed tomography-guided stereotactic adaptive radiotherapy (CT-STAR)
Authors: Kim Minsol , Schiff Joshua P. , Price Alex , Laugeman Eric , Samson Pamela P. , Kim Hyun , Badiyan Shahed N. , Henke Lauren E.
Published: September 2022

Background

Online adaptive stereotactic radiotherapy allows for improved target and organ at risk (OAR) delineation and inter-fraction motion management via daily adaptive planning. The use of adaptive SBRT for the treatment of pancreatic cancer (performed until now using only MRI or CT on rails-guided adaptive radiotherapy), has yielded promising outcomes. Herein we describe the first reported case of cone beam CT-guided stereotactic adaptive radiotherapy (CT-STAR) for the treatment of pancreatic cancer.

Case presentation

A 61-year-old female with metastatic pancreatic cancer presented for durable palliation of a symptomatic primary pancreatic mass. She was prescribed 35 Gy/5 fractions utilizing CT-STAR. The patient was simulated utilizing an end-exhale CT with intravenous and oral bowel contrast. Both initial as well as daily adapted plans were created adhering to a strict isotoxicity approach in which coverage was sacrificed to meet critical luminal gastrointestinal OAR hard constraints. Kilovoltage cone beam CTs were acquired on each day of treatment and the radiation oncologist edited OAR contours to reflect the patient’s anatomy-of-the-day. The initial and adapted plan were compared using dose volume histogram objectives, and the superior plan was delivered. Use of the initial treatment plan would have resulted in nine critical OAR hard constraint violations. The adapted plans achieved hard constraints in all five fractions for all four critical luminal gastrointestinal structures.

Conclusions

We report the successful treatment of a patient with pancreatic cancer treated with CT-STAR. Prior to this treatment, the delivery of ablative adaptive radiotherapy for pancreatic cancer was limited to clinics with MR-guided and CT-on-rails adaptive SBRT technology and workflows. CT-STAR is a promising modality with which to deliver stereotactic adaptive radiotherapy for pancreatic cancer.
Risk factors for posttraumatic empyema in diaphragmatic injuries
Authors: García Alberto Federico , Rodríguez Fernando , Sánchez Álvaro , Caicedo-Holguín Isabella , Gallego-Navarro Carlos , Naranjo María Paula , Caicedo Yaset , Burbano Daniela , Currea-Perdomo Diana Felisa , Ordoñez Carlos A. , Puyana Juan Carlos
Published: September 2022

Background

Penetrating diaphragmatic injuries are associated with a high incidence of posttraumatic empyema. We analyzed the contribution of trauma severity, specific organ injury, contamination severity, and surgical management to the risk of posttraumatic empyema in patients who underwent surgical repair of diaphragmatic injuries at a level 1 trauma center.

Methods

This is a retrospective review of the patients who survived more than 48 h. Univariate OR calculations were performed to identify potential risk factors. Multiple logistic regression was used to calculate adjusted ORs and identify independent risk factors.

Results

We included 192 patients treated from 2011 to 2020. There were 169 (88.0) males. The mean interquartile range, (IQR) of age, was 27 (22–35) years. Gunshot injuries occurred in 155 subjects (80.7%). Mean (IQR) NISS and ATI were 29 (18–44) and 17 (10–27), respectively. Thoracic AIS was > 3 in 38 patients (19.8%). Hollow viscus was injured in 105 cases (54.7%): stomach in 65 (33.9%), colon in 52 (27.1%), small bowel in 42 (21.9%), and duodenum in 10 (5.2%). Visible contamination was found in 76 patients (39.6%). Potential thoracic contamination was managed with a chest tube in 128 cases (66.7%), with transdiaphragmatic pleural lavage in 42 (21.9%), and with video-assisted thoracoscopy surgery or thoracotomy in 22 (11.5%). Empyema occurred in 11 patients (5.7%). Multiple logistic regression identified thoracic AIS > 3 (OR 6.4, 95% CI 1.77–23. 43), and visible contamination (OR 5.13, 95% IC 1.26–20.90) as independent risk factors. The individual organ injured, or the method used to manage the thoracic contamination did not affect the risk of posttraumatic empyema.

Conclusion

The severity of the thoracic injury and the presence of visible abdominal contamination were identified as independent risk factors for empyema after penetrating diaphragmatic trauma.
Systemic interleukin-6 inhibition ameliorates acute neuropsychiatric phenotypes in a murine model of acute lung injury
Authors: Anwar Faizan , Sparrow Nicklaus A. , Rashid Mohammad Harun , Guidry Gena , Gezalian Michael M. , Ley Eric J. , Koronyo-Hamaoui Maya , Danovitch Itai , Ely E. Wesley , Karumanchi S. Ananth , Lahiri Shouri
Published: September 2022

Acute neuropsychiatric impairments occur in over 70% of patients with acute lung injury. Mechanical ventilation is a well-known precipitant of acute lung injury and is strongly associated with the development of acute delirium and anxiety phenotypes. In prior studies, we demonstrated that IL-6 mediates neuropathological changes in the frontal cortex and hippocampus of animals with mechanical ventilation-induced brain injury; however, the effect of systemic IL-6 inhibition on structural and functional acute neuropsychiatric phenotypes is not known. We hypothesized that a murine model of mechanical ventilation-induced acute lung injury (VILI) would induce neural injury to the amygdala and hippocampus, brain regions that are implicated in diverse neuropsychiatric conditions, and corresponding delirium- and anxiety-like functional impairments. Furthermore, we hypothesized that these structural and functional changes would reverse with systemic IL-6 inhibition. VILI was induced using high tidal volume (35 cc/kg) mechanical ventilation. Cleaved caspase-3 (CC3) expression was quantified as a neural injury marker and found to be significantly increased in the VILI group compared to spontaneously breathing or anesthetized and mechanically ventilated mice with 10 cc/kg tidal volume. VILI mice treated with systemic IL-6 inhibition had significantly reduced amygdalar and hippocampal CC3 expression compared to saline-treated animals and demonstrated amelioration in acute neuropsychiatric behaviors in open field, elevated plus maze, and Y-maze tests. Overall, these data provide evidence of a pathogenic role of systemic IL-6 in mediating structural and functional acute neuropsychiatric symptoms in VILI and provide preclinical justification to assess IL-6 inhibition as a potential intervention to ameliorate acute neuropsychiatric phenotypes following VILI.
The CHALLENGE trial: the effects of a virtual reality-assisted exposure therapy for persistent auditory hallucinations versus supportive counselling in people with psychosis: study protocol for a randomised clinical trial
Authors: Smith L. C. , Mariegaard L. , Vernal D. L. , Christensen A. G. , Albert N. , Thomas N. , Hjorthøj C. , Glenthøj L. B. , Nordentoft M.
Published: September 2022

Background

Many patients suffering from schizophrenia spectrum disorders continue having distressing auditory hallucinations in spite of treatment with antipsychotic medication. The aim of this trial is to examine the effect of a targeted virtual reality therapy for persistent auditory hallucinations in individuals with psychosis. The trial explores whether this type of therapy can decrease the severity, frequency and distress of auditory hallucinations and, additionally, whether it can reduce clinical symptoms and enhance daily functioning in individuals with psychosis.

Methods

The study is a randomised, assessor-blinded parallel-group superiority clinical trial, allocating a total of 266 patients to either the experimental intervention or supportive counselling. The participants will be randomised to either (1) seven sessions of virtual reality therapy or (2) seven sessions of supportive counselling to be delivered within the first 12 weeks after inclusion in the study. All participants will be assessed at baseline and 12 and 24 weeks post-baseline. Independent assessors blinded to the treatment allocation will evaluate the outcome. The primary outcome is the level of auditory hallucinations measured with the Psychotic Symptoms Rating Scales (PSYRATS-AH) total score at the cessation of treatment at 12 weeks. Secondary outcomes are frequency of auditory hallucinations, the distress caused by auditory hallucinations, perceived voice power, patient acceptance of voices, patients’ ability to respond to voices in an assertive way and social and daily function.

Discussion

Promising evidence of the efficacy of this immersive virtual reality-based therapy for auditory hallucinations exist, but evidence needs to be established in a large, methodological rigorous trial. If the therapy proves to be beneficial in reducing the severity of refractory auditory hallucinations, a large group of patients with schizophrenia and related disorders could be the target group of this short-term psychotherapeutic intervention.
Landscape of the gut archaeome in association with geography, ethnicity, urbanization, and diet in the Chinese population
Authors: Bai Xiaowu , Sun Yang , Li Yue , Li Maojuan , Cao Zhirui , Huang Ziyu , Zhang Feng , Yan Ping , Wang Lan , Luo Juan , Wu Jing , Fan Dejun , Chen Hongxia , Zhi Min , Lan Ping , Zeng Zhong , Wu Xiaojian , Miao Yinglei , Zuo Tao
Published: September 2022

Background and aims

The human gut is home to a largely underexplored microbiome component, the archaeome. Little is known of the impact of geography, urbanization, ethnicity, and diet on the gut archaeome in association with host health. We aim to delineate the variation of the human gut archaeome in healthy individuals and its association with environmental factors and host homeostasis.

Methods

Using metagenomic sequencing, we characterized the fecal archaeomes of 792 healthy adult subjects from 5 regions in China, spanning 6 ethnicities (Han, Zang, Miao, Bai, Dai, and Hani), consisting of both urban and rural residents for each ethnicity. In addition, we sampled 119 host variables (including lifestyle, diet, and blood parameters) and interrogated the influences of those factors, individually and combined, on gut archaeome variations.

Results

Population geography had the strongest impact on the gut archaeome composition, followed by urbanization, dietary habit, and ethnicity. Overall, the metadata had a cumulative effect size of 11.0% on gut archaeome variation. Urbanization decreased both the α-diversity (intrinsic microbial diversity) and the β-diversity (inter-individual dissimilarities) of the gut archaeome, and the archaea-to-bacteria ratios in feces, whereas rural residents were enriched forMethanobrevibacter smithiiin feces. Consumption of buttered milk tea (a characteristic diet of the rural Zang population) was associated with increased abundance ofM. smithii.M. smithiiwas at the central hub of archaeal-bacterial interactions in the gut microecology, where it was positively correlated with the abundances of a multitude of short chain fatty acid (SCFA)-producing bacteria (includingRoseburia faecis,Collinsella aerofaciens, andPrevotella copri). Moreover, a decreased abundance ofM. smithiiwas associated with increased human blood levels of cholinesterase in the urban population, coinciding with the increasing prevalence of noncommunicable diseases (such as dementia) during urbanization.

Conclusions

Our data highlight marked contributions of environmental and host factors (geography, urbanization, ethnicity, and habitual diets) to gut archaeome variations across healthy individuals, and underscore the impact of urbanization on the gut archaeome in association with host health in modern society.
Assessing Japanese junior high school students’ English achievement through computer-based testing in the classroom: a case of integrated reading-into-writing continuous task
Authors: Niimi Noriyasu , Matsuura Nobukazu
Published: September 2022

Introduction

This paper describes the exploratory case and initial evaluation of the computer-based testing (CBT) prototype. The advantage of CBT over paper-based testing (PBT) is that it allows us to control the order of questions and provides test takers with continuous tasks capturing their thought processes. Additionally, their response process data such as response time (RT) can be obtained. Taking advantage of these, we created a CBT prototype in the classroom for Japanese junior high school students.

Case description

A CBT model was created to assess integrated reading and writing ability and was administered to 32 junior high school students. Their process achievement and the relation between the process response and writing quality were analyzed. Students’ RT for each screen was analyzed using hierarchical cluster analysis.

Discussion and evaluation

We identified not only students facing difficulties at each stage of a series of thought processes but also five clusters that include students spending too much time reading source texts or organizing their ideas. We suggest how CBT can be developed to identify students with difficulties and applied to teaching.

Conclusions

CBT has the possibility of detecting students who are able to complete the language performance task by controlling the order of answers, asking questions sequentially, and obtaining RT effectively.
Growing Financial Burden From High-Cost Targeted Oral Anticancer Medicines Among Medicare Beneficiaries With Cancer
Authors: Li Meng , Liao Kaiping , Pan I-Wen , Shih Ya-Chen Tina
Published: September 2022

PURPOSE:

The rapidly rising costs of targeted oral anticancer medicines (TOAMs) raise concerns over their affordability. Our goal was to examine recent trends in the uptake of TOAMs among cancer patients with Medicare Part D, the share of TOAM users who reached catastrophic coverage, and the annual spending on TOAMs in the catastrophic phase.

METHODS:

Using the 5% SEER-Medicare, we included patients age 65 years and older who had one primary cancer diagnosis between 2011 and 2016. We included person-years where patients were enrolled in a Part D plan for the entire year, did not receive the low-income subsidy at any time of the year, and received anticancer systemic therapies. We estimated the trends in the share of patients who used TOAMs, the percentage of TOAM users reaching catastrophic coverage, and the total and patient out-of-pocket spending on TOAMs in the catastrophic phase in a year.

RESULTS:

From 2011 to 2016, the uptake of TOAMs among our study population increased from 3.6% to 8.9%. The percentage of non–low-income subsidy TOAM users who reached catastrophic coverage increased from 54.6% to 60.3%. Among those who reached the catastrophic phase, mean total gross spending on TOAMs in the catastrophic phase increased from $16,074 (USD) to $64,233 (USD) and mean patient out-of-pocket spending from $596 (USD) to $2,549 (USD). The mean 30-day total spending increased from $4,011 (USD) to $8,857 (USD), and the mean 30-day out-of-pocket spending from $154 (USD) to $328 (USD).

CONCLUSION:

The high and growing burden from TOAMs highlighted the need for reining in drug prices and capping out-of-pocket spending.
Growth Patterns of Children With Short Stature in Adulthood According to Auxological Status and Maturity at Birth
Authors: Pfäffle Roland , Knüpfer Matthias , Göbert Melanie , Vogel Mandy , Gausche Ruth , Beger Christoph , Keller Eberhard , Körner Antje , Thome Ulrich , Kiess Wieland
Published: September 2022

Context

Prematurity carries a risk for impaired postnatal growth and long-term growth restriction. Especially children born SGA seem vulnerable for poor growth, as a persistent short stature can be observed in app 10-15% of these children.

Objective

In this study we aimed to recognize differences in growth patterns of children according to sex, maturity, and auxological status at birth facilitating earlier identification of small-for-gestational-age (SGA) children with adult short stature.

Methods

The growth data of 44 791 infants born between January 1, 1980, and December 30, 2012, among 2 pediatric cohorts with follow-up through December 31, 2020, were analyzed. A total of 5698 children with birth data had measurements at near final height (nfh) and at least 2 further points.

Results

Preterm children (gestational age < 37 weeks) had a significantly lower mean nfh SDS than term children (preterm, −0.61; term, −0.18) and a higher likelihood of nfh < third percentile (preterm, 20.5%; term, 12.2%). SGA born children also had a lower mean nfh SD score (SDS) than children born appropriate for gestational age (AGA) (SGA, −1.06; AGA, −0.15) and a higher likelihood of nfh < third percentile (SGA, 28.2%; AGA 10.1%). Of 1204 SGA children, 672 (56%) showed successful catch-up growth (CUG) to nfh greater than or equal to the 10th percentile (SGA-CU), and 532 children (44%) did not (SGA-S). The difference in their mean nfh SDS (SGA-CU, −0.12; SGA-S −2.26) can only partly be explained by the differences in mean mid-parental height SDS (SGA-CU, −0.3; SGA-S, −1.19). During the first year, SGA-CU showed higher CUG (SGA-CU, +1.2 SDS; SGA-S, +0.45 SDS), which helps to discriminate between groups earlier.

Conclusion

Final growth outcome was influenced by prematurity and auxological status at birth, but not by sex. Height/length SDS increments during year 1 are instrumental to discern SGA children with later normal or short stature. While observing CUG until year 2 and 3 can add specificity, discrimination thereafter becomes difficult.
Thyroid Hormone–mediated Histone Modification Protects Cortical Neurons From the Toxic Effects of Hypoxic Injury
Authors: Abe Kiyomi , Li Jianrong , Liu Yan Yun , Brent Gregory A
Published: September 2022

Context

Thyroid hormone has been shown to have a protective role in neuronal injury, although the mechanisms have not been established. The cellular response to stress that promotes adaptation and survival has been shown to involve epigenetic modifications.

Objective

We hypothesized that the neuroprotective role of thyroid hormone was associated with epigenetic modifications of histone proteins. We used hypoxic neurons as a model system for hypoxia-induced brain injury.

Methods

Mouse primary cortical neurons were exposed to 0.2% oxygen for 7 hours, with or without, treatment with triiodothyronine (T3). We analyzed the expression of histone-modifying enzymes by RNA-seq and the post-translationally modified histone 3 proteins by enzyme-linked immunosorbent assay (ELISA) and Western blot.

Results

We found that methylation of H3K27, associated with inactive promoters, was highly induced in hypoxic neurons, and this histone methylation was reduced by T3 treatment. H3K4 methylation is the hallmark of active promoters. The expression of 3 (Set1db, Kmta2c, and Kmt2e) out of 6 H3K4 methyltransferases was downregulated by hypoxia and expression was restored by T3 treatment. H3K4me3 protein, measured by ELISA, was increased 76% in T3-treated hypoxic neurons compared with the levels without T3 treatment. H3K56ac plays a critical role in transcription initiation and was markedly increased in T3-treated hypoxic neurons compared with those without T3 treatment, indicating stimulation of gene transcription. Additionally, T3 treatment restored hypoxia-induced downregulation of histone acetyltransferase, Kat6a, Kat6b, and Crebbp, which function as transcription factors.

Conclusion

These findings indicate that T3 treatment mitigates hypoxia-induced histone modifications and protects neurons from hypoxia-induced injury.
Mice With RIP-Cre–mediated Deletion of the Long Noncoding RNA Meg3 Show Normal Pancreatic Islets and Enlarged Pituitary
Authors: Parekh Vaishali I , Sun Hui , Chen Min , Weinstein Lee S , Agarwal Sunita K
Published: September 2022

Context

Maternally expressed gene 3 (MEG3) is a long noncoding RNA (lncRNA) that has been implicated as a tumor suppressor.

Objective

The expression of MEG3 RNA is downregulated in various human tumors, including pituitary adenoma and pancreatic islet tumors due to MEG3 gene deletion or DNA hypermethylation. Mouse models with conventional germline deletion of Meg3 have shown that Meg3 is essential for perinatal or postnatal development and survival. However, a direct role of Meg3 loss in tumorigenesis has not been shown.

Methods

To observe a causal relationship between Meg3 loss and tumorigenesis, we have generated a mouse model with conditional deletion of Meg3 mediated by the RIP-Cre transgene that initiated Meg3 deletion in pancreatic islet β cells and anterior pituitary.

Results

Meg3 loss did not lead to the development of islet tumors. Interestingly, RIP-Cre–mediated Meg3 loss led to the development of an enlarged pituitary. The genes in the Meg3 region are transcribed together as a 210 kb RNA that is processed into Meg3 and other transcripts. Whether these tandem transcripts play a functional role in the growth of pancreatic endocrine cells and pituitary cells remains to be determined.

Conclusion

Our mouse model shows that Meg3 loss leads to hyperplasia in the pituitary and not in pancreatic islets, thus serving as a valuable model to study pathways associated with pituitary cell proliferation and function. Future mouse models with specific inactivation of Meg3 alone or other transcripts in the Meg3 polycistron are warranted to study tissue-specific effects on initiating neoplasia and tumor development.
Legacies of War
Authors: Theidon Kimberly
Published: September 2022

In Legacies of War Kimberly Theidon examines the lives of children born of wartime rape and the experiences of their mothers and communities to offer a gendered theory of harm and repair. Drawing on ethnographic research in postconflict Peru and Colombia, Theidon considers the multiple environments in which conception, pregnancy, and childbirth unfold. She reimagines harm by taking into account the impact of violence on individual people as well as on more-than-human lives, bodies, and ecologies, showing how wartime violence reveals the interdependency of all life. She also critiques policy makers, governments, and humanitarian organizations for their efforts at postconflict justice, which frequently take an anthropocentric rights-based approach that is steeped in liberal legalism. Rethinking the intergenerational reach of war while questioning what counts as sexual and reproductive violence, Theidon calls for an explicitly feminist peace-building and postconflict agenda that includes a full range of sexual and reproductive rights, including access to safe and affordable abortions.
Mural Wnt/β-catenin signaling regulates Lama2 expression to promote neurovascular unit maturation
Authors: Biswas Saptarshi , Shahriar Sanjid , Giangreco Nicholas P. , Arvanitis Panos , Winkler Markus , Tatonetti Nicholas P. , Brunken William J. , Cutforth Tyler , Agalliu Dritan
Published: September 2022

Neurovascular unit and barrier maturation rely on vascular basement membrane (vBM) composition. Laminins, a major vBM component, are crucial for these processes, yet the signaling pathway(s) that regulate their expression remain unknown. Here, we show that mural cells have active Wnt/β-catenin signaling during central nervous system development in mice. Bulk RNA sequencing and validation using postnatal day 10 and 14 wild-type versus adenomatosis polyposis coli downregulated 1 (Apcdd1−/−) mouse retinas revealed that Lama2 mRNA and protein levels are increased in mutant vasculature with higher Wnt/β-catenin signaling. Mural cells are the main source of Lama2, and Wnt/β-catenin activation induces Lama2 expression in mural cells in vitro. Markers of mature astrocytes, including aquaporin 4 (a water channel in astrocyte endfeet) and integrin-α6 (a laminin receptor), are upregulated in Apcdd1−/− retinas with higher Lama2 vBM deposition. Thus, the Wnt/β-catenin pathway regulates Lama2 expression in mural cells to promote neurovascular unit and barrier maturation.
Investigation of the Relationship Between the Morphology of the Toe Flexor Muscles in Ballet Dancers and the Postural Stability During Standing on Demi-Pointe: A Cross-Sectional Study
Authors: Ishihara Honoka , Maeda Noriaki , Komiya Makoto , Tashiro Tsubasa , Urabe Yukio
Published: September 2022

Introduction: This study investigated how toe flexor muscles are related to postural stability in 11 ballet dancers and 12 non-dancers.
 Methods: Toe flexor strength (TFS), cross-sectional areas (CSA) of the abductor hallucis, flexor hallucis brevis, flexor digitorum brevis, flexor hallucis longus (FHL), and flexor digitorum longus, and center of pressure (COP) displacement during single-leg demi-pointe were measured. Correlations between toe flexor strength and COP displacement and between CSA and COP displacement within each group were calculated using Pearson's correlation coefficient or Spearman's correlation coefficient.
 Results: The dancers showed smaller COP displacement than the non-dancers (p < 0.05). Toe flexor strength in dancers was moderately negatively correlated with COP displacement in the anterior-pos- terior direction (r = -0.54, p < 0.01) and total COP displacement (r = -0.57, p < 0.01). Only the CSA of the FHL in dancers exhibited a significant negative correlation with COP displacement in the anterior-posterior direction (r = -0.42, p < 0.05) and total COP displacement (r = -0.52, p < 0.01).
 Conclusion: The present study found a relationship between the toe flexor strength and COP displacement and CSA of toe flexor muscles and COP displacement during one-legged demi-pointe standing. These results suggest that the development of the toe flexor muscles may be involved in the balance control of dancers.
Variability of early autumn planktonic assemblages in the strait of Gibraltar: a regionalization analysis
Authors: VALCÁRCEL-PÉREZ NEREA , RAMÍREZ-ROMERO EDUARDO , GARCÍA CARLOS M. , GONZÁLEZ-GORDILLO JUAN IGNACIO , ECHEVARRÍA FIDEL
Published: September 2022

The Strait of Gibraltar (SG) is the only connection of the Mediterranean Sea with the global circulation. The SG is an outstanding marine region to explore physical-biological coupling of pelagic communities due to its hydrodynamic complexity, including strong tidal forcing and marked spatial gradients and fronts. The authors have unravelled the role of the fortnightly tidal scale (spring and neap tides) and local processes (upwelling and tidal-topographic mixing) that shape planktonic assemblages in the Strait. To do so, an oceanographic cruise was taken in early autumn 2008 with a high-resolution grid sampling and spring/neap tidal conditions. The planktonic features were captured using different automatic and semi-automatic techniques of plankton analyses (flow cytometry, FlowCAM, LOPC and Ecotaxa) that allowed covering a wide range of sizes of the community from pico- to mesoplankton. The SG was sectorized into two clusters based on the biogeochemical and main water column properties. Cluster 1 (CL1) covered shallow productive areas around Cape Trafalgar (CT). CL1 presented higher concentrations of chlorophyll and nutrients, and phytoplankton was mostly represented by Synechococcus and coastal diatoms while zooplankton had the highest percentage of meroplankton (31%). In contrast, cluster 2 (CL2) covered open ocean waters and presented more oligotrophic features, i.e. nitrogen-depleted waters with lower chlorophyll concentrations and a picoplankton community dominated by Prochlorococcus and holoplankton predominance in mesozooplankton. Under early autumn conditions with overall nutrient-depleted and stratified waters, the CT area emerges as an ecosystem where the constant tidal mixing and nutrients supply is coupled with an active production also being favored by high residence times and finally shaping a plankton community with unique features in the area.
Preservation of heritage buildings in Alexandria, Egypt: an application of heritage digitisation process phases and new documentation methods
Authors: El Menshawy Adel , Omar Walid , El Adawy Sherif
Published: September 2022

Background: Throughout the history of the city, the architecture of Alexandria, Egypt, has been in contact with world cultures, especially those of the Mediterranean sphere. Alexandria is rich with cultural features dating back seven thousand years. In Alexandria, the heritage value of the city has decreased because there is no suitable documentation system for these more recent assets. The development of a new technique for preserving heritage buildings is required. For example, image- based techniques can gather data using photography, panoramic photography, and close-range photogrammetry. In this research, we primarily seek to implement Heritage Digitisation Process Phases (HDPP) and establish new documentation methods in architectural conservation and built-heritage preservation, i.e., Virtual Reality (VR) and Website Heritage Documentation (WHD).

Methods: The methodology is designed to preserve and manage cultural heritage using HDPP for the promotion of heritage building preservation in Alexandria.

Results: The results show that the application of HDPP has led to the creation of a digital database about the Société Immobilière building, which was chosen as a case study for this research.

Conclusions: Implementation of HDPP and usage of new documentation methods i.e., VR and WHD create a digital path to help strengthen its image and connect the place to users, recreational areas are created to communicate and explore the city’s architectural history.
Case Report: Sarcoidosis
Authors: Twayana Anu , Deo Sulav , Poudel Saroj , Shrestha Bishayeeta , Dhakal Sirish , Rimal Sabin , Sapkota Prakash
Published: September 2022

Sarcoidosis is a chronic granulomatous disease with multisystem involvement and can present with vague symptoms, so the degree of suspicion should be high. Sarcoidosis has a wide range of clinical symptoms, owing to its multisystem involvement. The lungs, peripheral lymphatics, skin, liver, eye, spleen, bone, salivary glands, joints, and heart are the most commonly involved organ systems pathologically. Sarcoidosis often manifests in the fourth decade of life, but it might occasionally manifest in later years. We present a case of 69-year-old woman who initially complained of generalized weakness, fatigue, and joint pain which later progressed to pulmonary and cutaneous symptoms including cough, dyspnea, chest discomfort, and skin nodules. Examination revealed right cervical lymphadenopathy, bilateral basal crackles in lungs, non-tender nodules over the dorsum of bilateral forearm and hand along with erythema nodosum on bilateral legs. Chest radiograph and computed tomography scans were typical of sarcoidosis. Biopsy of the lymph node revealed noncaseating granuloma and serum angiotensinogen converting enzyme level was raised. Treatment was started with 40 mg prednisolone daily and tapered over a year. The patient had clinical and radiological improvement over the duration of therapy and was on regular follow-up with routine investigations. Clinically, the patient is doing well at follow-up. A high degree of suspicion, familiarity with imaging features, and prompt treatment in selected cases may help in diagnosing, evaluating the extent of disease, and guiding optimal health care.
La generación hiperconectada
Authors: Robayo Pinzon Oscar , Páez Torres Magda
Published: September 2022

Los teléfonos inteligentes se han convertido en los reyes de un mundo permanentemente conectado en el que se volvió costumbre, y casi una necesidad, responder a los estímulos de la realidad virtual. De acuerdo con un estudio de la Universidad del Rosario, junto con otras instituciones, las aplicaciones de mensajería instantánea y las redes sociales son las que mayor impulsividad generan entre los jóvenes.
Digitalizar, georreferenciar, visualizar y narrar la ciudad. Usos del suelo y orden urbano: Bogotá, 1894
Authors: Colón Llamas Luis Carlos , Picón Rodríguez Anthony
Published: September 2022

El artículo propone reflexionar en torno a las humanidades, la historia espacial y algunas expe­riencias que han combinado datos, mapas antiguos y sistemas digitales para la georreferenciación de fuentes y su visualización en mapas. Se argumenta que estas herramientas y su uso en la historia espacial tienen un gran potencial para enriquecer la comprensión sobre la historia de la ciudad, no solo a partir de las nuevas posibilidades en el manejo y organización de fuentes, sino también mediante las formas de análisis y colaboración que permiten los nuevos escenarios de las narrativas espaciales. Con ello se evidencian tanto las vías metodológicas que han abierto estas herramientas, como los desafíos a futuro que les plantean a quienes quieran hacer uso de ellas.
Price Discrimination and Inventory Allocation in Bertrand Competition
Authors: Cohen Maxime C. , Jacquillat Alexandre , Song Haotian
Published: September 2022

Problem definition: It is common practice for firms to deploy strategies based on customer segmentation (by clustering customers into different segments) and price discrimination (by offering different prices to different customer segments). Price discrimination, although seemingly beneficial, can hurt firms in competitive environments. Academic/practical relevance: It is thus critical for firms to understand when to engage in price discrimination and how to support discriminatory pricing practices with appropriate inventory management strategies. This paper tackles this overarching question through operational lenses by studying the joint impact of price discrimination and the allocation of limited inventory across customer segments. Methodology: We develop a Bertrand competition game featuring capacity restrictions, quality differentiation, and customer heterogeneity. Results: We characterize (pure- or mixed-strategy) Nash equilibria for a single-stage game reflecting uniform pricing and for a two-stage inventory-price game reflecting discriminatory pricing along with endogenous inventory allocation. Managerial implications: We identify three sources of market friction in price competition enabling firms to earn higher profits: capacity limitations, quality differentiation, and customer heterogeneity. Price discrimination eliminates the market frictions from customer heterogeneity, but strategic inventory allocation restores (or strengthens) the market frictions from capacity limitations. As such, price discrimination is only beneficial when combined with optimal inventory allocation across segments. We discuss relevant real-world examples featuring regional price discrimination along with strategic inventory allocation, including fast fashion and vaccines. Otherwise, uniform pricing may outperform discriminatory pricing. Our results thus underscore the critical role of inventory allocation in the design of competitive pricing strategies.

Funding: This research was partially supported by the National Natural Science Foundation of China [Grant 71821002].

Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2022.1146 .
“Dear CEO and Board”: How Activist Investors’ Confidence in Tone Influences Campaign Success
Authors: Brauer Matthias , Wiersema Margarethe , Binder Philipp
Published: September 2022

Activist hedge funds represent the most potent form of financial activism. Yet we do not fully understand how these activist investors, despite holding only a small stake in target firms, are able to influence management and the board to acquiesce to their demands, especially given the large uncertainty that their demands will improve shareholder value. Building on impression management (IM) theory, we propose that activist investors who express their concerns and demands with high confidence in their letters to target firms are likely to be perceived as knowledgeable and competent by the firm’s other shareholders, thus influencing the response of the firm’s management and board. In support of this theoretical proposition, results of our empirical analysis of 475 U.S. activist campaigns against U.S. companies between 2007 and 2019 suggest that confidence in tone in an activist’s letter, as a form of self-promotion, is positively associated with campaign success. We also observe that the positive association between confidence in tone in activist letters and campaign success is less for activists with greater success in prior campaigns and in campaigns with multiple activists. Our paper contributes to financial activism research by showing that activists’ verbal impression management can serve as an effective influence tactic in their campaigns. Our study also contributes to the emerging research stream on verbal IM by introducing a language attribute, confidence in tone, that has not been studied in management research and is distinct from past constructs examined in verbal IM research.
Suprascapular nerve blockage for painful shoulder pathology – a systematic review and meta-analysis of treatment techniques
Authors: Batten TJ , Evans JP , Burden EG , Mak WK , White W , Smith CD
Published: September 2022

Background

Suprascapular nerve blockade (SSNB) through injection (SSNBi) and/or pulsed radiofrequency (PRF) provide options for the management of painful shoulder pathology. Multiple techniques for delivery of SSNB are described but no consensus on optimal symptom control is available. This systematic review and meta-analysis aims to assess patient-focussed outcomes in SSNB and explore the impact of variation in the technical application of this treatment modality.

Methods

MEDLINE, Embase and CINAHL were searched for case series, cohort studies and randomised control trials published from database inception until 28 January 2021. Articles reporting use of SSNBi or PRF for treatment of shoulder pain with a minimum 3 months follow-up were included. Patient-reported outcome measures (PROMs) were extracted and the pooled standardised mean difference (SMD), weighted by study size, was reported. Quality of methodology was assessed using Wylde’s nonsummative four-point system.

Findings

Of 758 references, 18 studies were included, totalling 704 SSNB. Average pain improvement at 3 months was 52.3%, with meta-analysis demonstrating a SMD of 2.37. Whereas SSNBi combined with PRF shows the greatest SMD of 2.75, this did not differ significantly from SSNBi or PRF when used as monotherapy. Location of treatment and the guidance technique used did not influence outcome.

Conclusion

SSNBi and PRF provide safe and effective treatment for shoulder pain, as judged by PROMs. This may be of particular value in aging or comorbid patients and with surgical restrictions during the COVID-19 pandemic. Regardless of technique, patients experience a marked improvement in pain that is maintained beyond 3 months.
Biological Cells as Natural Biophotonic Devices: Fundamental and Applications–introduction to the feature issue
Authors: Ferraro Pietro , Li Yuchao , Miccio Lisa , Shui Lingling , Zhang Yao
Published: September 2022

This feature issue of Biomedical Optics Express presents a cross-section of interesting and emerging work of relevance to the use of biological cells or microorganisms in optics and photonics. The technologies demonstrated here aim to address challenges to meeting the optical imaging, sensing, manipulating and therapy needs in a natural or even endogenous manner. This collection of 15 papers includes the novel results on designs of optical systems or photonic devices, image-assisted diagnosis and treatment, and manipulation or sensing methods, with applications for both ex vivo and in vivo use. These works portray the opportunities for exploring the field crossing biology and photonics in which a natural element can be functionalized for biomedical applications.
Long-Range Distributed Acoustic Sensor Based on 3x3 Coupler Assisted Passive Demodulation Scheme
Authors: Türker Volkan , Uyar Faruk , Kartaloğlu Tolga , Özbay Ekmel , Özdür İbrahim
Published: September 2022

A distributed acoustic sensor based on phase-sensitive optical time domain reflectometry (-OTDR) and passive 3x3 coupler demodulation is demonstrated which is capable of quantifying strain perturbations at 40 km of a sensing fiber.
Non-invasive and Online Pipeline Corrosion Detection based on Distributed Acoustic Sensing
Authors: Yan Baoqiang , Zhang Keqing , Li Hao , Zhang Shixiong , Fan Cunzheng , Yan Zhijun , Sun Qizhen
Published: September 2022

A non-invasive online method for pipeline corrosion detection based on active acoustic flaw detection is proposed and demonstrated. The test results show that the proposed method can identify corrosion with a size less than 0.5%.