bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Hydrocarbon Burns: Considering Mental Health and Biochemical Abnormalities
Authors: Rudduck Emma-Leigh , Concannon Elizabeth , Coghlan Patrick , Govindan Thiru , Kurmis Rochelle , Solanki Nicholas
Published: January 2022

Volatile substance misuse, particularly the inhalation of hydrocarbons, is a growing issue globally. Consequences of volatile substance misuse, both acute and chronic cause cardiovascular, respiratory, renal, metabolic, and central nervous system damage. Whilst the effects of hydrocarbon abuse have been reported, the combination of intoxication with hydrocarbon and burns sustained has not yet been presented. A retrospective case series of patients who presented in the last 5 years to the Royal Adelaide Hospital with hydrocarbon-related burns in the context of illicit use was undertaken. Our aims are to present to the wider scientific community the high morbidity and mortality of hydrocarbon burn injuries and why this tertiary Burns Unit feel it most appropriate to medically stabilize these patients prior to definitive surgery for their burn. All patients that presented with acute hydrocarbon intoxication and sustained concomitant burns had significant psychiatric disorder and substance abuse history and three of five had either not eaten in several days resulting in acute malnourishment, refeeding syndrome or had evidence of chronic malnourishment with deranged electrolytes and hypoalbuminemia. Their definitive burns surgery was delayed where appropriate in order to facilitate medical stabilization as they were too high risk of cardiac membrane instability, electrolyte derangement, and/or respiratory compromise to undergo safe general anesthetic and burns debridement. We propose a multidisciplinary team approach, utilizing not only our Burns Unit care model of physiotherapists, psychologists, social work, and burns trained nurses and surgeons but also Intensive Care, Toxicology, Addiction medicine and General Medical physicians in the management of these patients.
A Retrospective Review of Emergency Department Visits That May Be Appropriate for Management in Non-Emergency Settings
Authors: Tapia Ashley D , Howard Jeffrey T , Bebo Natasha L , Pfaff James A , Chin Eric J , Trueblood Wesley A , April Michael D , Long Brit J , Long Adrianna N , Fernandez William G , Schauer Steven G
Published: January 2022

Background

Emergency departments (EDs) continue to struggle with overcrowding, increasing wait times, and a surge in patients with non-urgent conditions. Patients frequently choose the ED for non-emergent medical issues or injuries that could readily be handled in a primary care setting. We analyzed encounters in the ED at the Brooke Army Medical Center—the largest hospital in the Department of Defense—to determine the percentage of visits that could potentially be managed in a lower cost, appointment-based setting.

Materials and Methods

We conducted a retrospective chart review of patients within our electronic medical record system from September 2019 to August 2020, which represented equidistance from the start of the COVID-19 pandemic, resulting in a shift in ED used based on previously published data. Our study also compared the number of ED visits pre-covid vs. post-covid. We defined visits to be primary care eligible if they were discharged home and received no computed tomography imaging, ultrasound, magnetic resonance imaging, intravenous medications, or intramuscular-controlled substances.

Results

During the 12 month period, we queried data on 75,205 patient charts. We categorized 56.7% (n = 42,647) of visits as primary care eligible within our chart review. Most primary-care-eligible visits were ESI level 4 (59.2%). The largest proportion of primary-care-eligible patients (28.3%) was seen in our fast-track area followed by our pediatric pod (21.9%). The total number of ED visits decreased from 7,477 pre-covid to 5,057 post-covid visits. However, the proportion of patient visits that qualified as primary care eligible was generally consistent.

Conclusions

Over half of all ED visits in our dataset could be primary care eligible. Our findings suggest that our patient population may benefit from other on-demand and appointment-based healthcare delivery to decompress the ED.
One-loop contributions to the decay H → νl̅νlγ in the Standard Model revisited
Authors: Phan Khiem Hong , Tran Dzung Tri
Published: January 2022

One-loop contributions to the decay H → νl̅νlγ with l = e, μ, τ within the Standard Model framework are revisited in this paper. We derive two representations for the form factors in this calculation. As a result, the computations are not only checked numerically by verifying the ultraviolet finiteness of the results but also confirming the ward identity of the amplitude. We find that the results have good stability with varying ultraviolet cutoff parameters as well as satisfying the ward identity. In phenomenological results, we study the partial decay widths for the decay channels in the two cases of the detected photon and invisible photon. Differential decay widths are also generated as a function of the energy of the final photon.
Effect of vitamin D source and dietary cation–anion difference in peripartum dairy cows on calcium homeostasis and milk production
Authors: Beck Matthew R , Zapalac Dakota , Chapman James D , Zanzalari K P , Holub Glenn A , Bascom Scott S , Engstrom Mark A , Reuter R Ryan , Foote Andrew P
Published: January 2022

The objective of this experiment was to determine the effects of dietary vitamin D source on serum calcium (Ca), urinary Ca excretion, and milk production when fed in combination with a prepartum acidogenic negative dietary cation–anion difference (DCAD) diet. Nonlactating, pregnant multiparous cows (n = 15), balanced for breed (Holstein n = 9 and Jersey n = 6), and previous mature equivalent milk production, were assigned to one of three treatments (five cows/treatment), consisting of a control (PCH; positive DCAD, 8.9 mEq/100 g DM) and two negative DCAD diets (−15.4 mEq/100 g DM), one with vitamin D3 (cholecalciferol; NCH) and one with 25-hydroxyvitamin D3 (calcidiol; NCA; DSM nutritional products). The treatments were formulated to provide 1.95 mg/d of vitamin D and were fed 28 d prior to expected calving date. Delivery of vitamin D sources was accomplished by manufacture of a pellet and 2 kg of these pellets were individually fed simultaneously each day along with 2 kg of ground corn daily at 0800 hours. Negative DCAD treatments were formulated to provide 0.46 kg/d of Animate (Phibro Animal Health) and, if needed, additional Animate was top-dressed at each feeding to achieve a urine pH between 5.5 and 6.0 based on the previous day’s urine pH. Close-up cows had ad libitum access to chopped bermudagrass (Cynodon dactylon L.) hay and hay intake was measured using SmartFeed Pro systems (C-Lock Inc.; Rapid City, SD). Prepartum urine and serum samples were collected weekly and serum was collected 36, 48, and 72 h post-calving. Prepartum dry matter intake (DMI) as a percent of body weight was not (P = 0.66) affected by treatments. Cows fed NCH and NCA had greater (P = 0.02) prepartum serum Ca than PCH and tended to have greater urinary Ca excretions (P = 0.10). Average postpartum serum Ca (mg/dL) was greater (P = 0.05) for cows fed NCH (8.8) compared with PCH (7.8), whereas NCA (8.4) was numerically intermediate and not (P > 0.05) different from either of the other treatments. Postpartum DMI was not affected by treatment (P = 0.39). Daily milk yield (MY) (kg/d) was greatest (P < 0.01) for NCA (37.5) compared with the other treatments and NCH (34.1) was intermediate and greater than PCH (29.9). These results suggest that an acidogenic prepartum diet in combination with vitamin D was effective in maintaining peripartum serum Ca and the 25-hydroxy form of vitamin D improved MY compared with NCH in early lactation.
Genetic Analysis of Pediatric Pancreatoblastoma
Authors: Wang Zhengzheng , Li Xiaoting , Li Qingjun , Zhou Jinxue
Published: January 2022

Pediatric pancreatoblastoma (PBL) is a rare disease, and the treatment of which is diverse. The molecular alteration in pancreatoblastoma is not very clear. A 7-year-old female who presented with intermittent abdominal pain, anorexia, and abdominal mass was admitted in our hospital. Pancreaticoduodenectomy, cholecystectomy, and retroperitoneal lymph node dissection were conducted. Immunohistochemistry results after surgery showed creatine kinase +, clusters differentiation 56 −, clusters differentiation 99 +, carcinoembryonic antigen −, periodic acid-Schiff +, B- catenin +, Ki-67 + 70%, progesterone receptor +, neuron-specific enolase −, vimentin −, and insulin −. According to the cell shape and the results of immunohistochemistry, the patient was diagnosed with PBL. The tumor tissue, adjacent tissue, and blood were collected. Mutation profiles were detected using next-generation sequencing technique with a panel of 704 genes. The child recovered well without complications postoperatively. There were 261 genes mutated in her plasma or tumor tissue (mutant frequency ≥1%). The adjacent tissue and plasma harbored the echinoderm microtubule-associated protein-like 4 gene-anaplastic lymphoma kinase fusion and tumor tissue harbored proto-oncogene receptor tyrosine kinase 1-solute carrier family 34 member A2 fusion. The gene alteration profiles of PBL patients warrant further investigations, which may provide new insight into the treatment of this disease.
Molecular Alterations in Solid Pseudopapillary Neoplasm of the Pancreas
Authors: Ghio Michael , Vijay Adarsh
Published: January 2022

Solid pseudopapillary neoplasms of the pancreas are overwhelmingly benign tumors predominately observed in women in the third decade of life. However, their malignant potential, based on local recurrences and metastases, has brought into question the available evidence on their biological behavior. Solid pseudopapillary neoplasms have distanced themselves from other pancreatic tumors with varying morphological appearance, immune profile, and histogenesis. In review of the literature, PubMed was queried using search strings, including “solid pseudopapillary neoplasm” and “molecular,” and “immunohistochemistry.” Alternative searches were also conducted given the variability in tumor name, including “solid pseudopapillary tumor” and “Frantz tumor.” This article provides an in-depth review into the molecular pathways that contribute to the pathogenesis of solid pseudopapillary neoplasms. It also discusses the implications of existing molecular pathways toward tumor aggressiveness and recurrence potential.
Identification of 2 Chinese Primary Pancreatic Ductal Adenocarcinoma Cancer Cell Lines and Their Phenotypes
Authors: Wang Jianxin , Li Enliang , Chen Qi , Wei Tao , Zhang Qi , Fu Qihan , Lou Yu , Wang Yi , Chen Yiwen , Bai Xueli , Liang Tingbo
Published: January 2022

Objectives

Pancreatic cancer (PC) is one of the most lethal cancers. Currently, the most commonly used PC cell lines were all derived from White individuals, and few models can be used to study in Asian populations. In China, the incidence of PC is increasing every year, highlighting the need to develop new Chinese PC cell lines for cancer research.

Methods

A total of 203 patients diagnosed with PC, enrolled from January 2012 to December 2017 in our hospital (Department of Hepatobiliary and Pancreatic Surgery), had received surgery. Primary PC patient tumor samples were harvested sterilely from surgery, minced, and digested in collagenase. Cells were cultured in plates precoated with l-polylysine.

Results

Two primary PC cell lines, Si-Liang 187 and Si-Liang 188, were established, both of which grew as adherent monolayers and demonstrated distinguished phenotypes. Si-Liang 187 shows the typical mesenchymal pattern, whereas Si-Liang 188 shows epithelial phenotype. Moreover, they carry different genetic backgrounds according to whole exome sequencing.

Conclusions

Two new Chinese PC cell lines were established, both of which were characterized and confirmed with high tumorigenicity. They may serve as useful tools for pathogenesis research when evaluating new treatment strategies in Asian patients.
Adult Proinsulinomatosis Associated With a MAFA Germline Mutation as a Rare Cause of Recurrent Hypoglycemia
Authors: Mintziras Ioannis , Peer Katharina , Goerlach Jannis , Goebel Joachim N. , Ramaswamy Annette , Slater Emily P. , Kann Peter Herbert , Bartsch Detlef Klaus
Published: January 2022

Sporadic adult insulinomatosis is an extremely rare clinical condition. Adult proinsulinomatosis has not yet been described. We report the case of a 48-year-old female patient with recurrent hypoglycemia caused by benign proinsulin-secreting pancreatic neuroendocrine neoplasias (pNENs) with no history of multiple endocrine neoplasia type 1. Initial workup revealed elevated serum proinsulin levels and a positive fasting test. Magnetic resonance imaging and endosonography visualized 2 pNENs in the pancreatic body and tail that were treated by robotic-assisted enucleation. After initial biochemical cure, the patient's hypoglycemia recurred 3 months after surgery. Imaging showed a new lesion in the pancreatic body, so that now a spleen-preserving subtotal distal pancreatectomy was performed. The pathological examination revealed 17 neuroendocrine microadenomas and 1 well-differentiated pNEN (Ki-67% 1%–2%) of 22-mm size as well as more than 200 (pro)insulin-producing β-cell precursor lesions, confirming the diagnosis of adult proinsulinomatosis. Mutation analysis of the germline DNA identified the in-frame deletion mutation (p.His207del) in the MAFA gene on chromosome 8. The patient was biochemically cured 16 months after the last surgical resection. Similarly to adult insulinomatosis, the presence of proinsulin-secreting tumors causes recurrent hypoglycemia and might be associated with germline mutations in the MAFA gene.
Magnetic Resonance Imaging–Based Radiomics Models to Predict Early Extrapancreatic Necrosis in Acute Pancreatitis
Authors: Zhou Ting , Xie Chao-lian , Chen Yong , Deng Yan , Wu Jia-long , Liang Rui , Yang Guo-dong , Zhang Xiao-ming
Published: January 2022

Objective

The aim of the study was to investigate radiomics models based on magnetic resonance imaging (MRI) for predicting early extrapancreatic necrosis (EXPN) in acute pancreatitis.

Methods

Radiomics features were extracted from T2-weighted images of extrapancreatic collections and late arterial-phase images of the pancreatic parenchyma for 135 enrolled patients (94 in the primary cohort, including 47 EXPN patients and 41 in the validation cohort, including 20 EXPN patients). The optimal features after dimension reduction were used for radiomics modeling through a support vector machine. A clinical model, the MR severity index score, and extrapancreatic inflammation on MRI were evaluated.

Results

Twelve optimal features from the extrapancreatic collection images and 10 from the pancreatic parenchyma images were selected for modeling. The pancreatic parenchyma-based and extrapancreatic collection-based radiomics models showed good predictive accuracy in both the training and validation cohorts. The areas under the curve of the extrapancreatic collection-based radiomics model (0.969 and 0.976) were consistent with those of the pancreatic parenchyma-based model (0.931 and 0.921) for both cohorts and better than those of the clinical model and imaging scores for both cohorts.

Conclusions

The MRI-based radiomics models of both the extrapancreatic collections and the pancreatic parenchyma had excellent predictive performance for early EXPN.
Surgical Intervention Strategies of Necrotizing Pancreatitis With Abdominal Compartment Syndrome
Authors: Kao Shih-Yi , Chen Tien-Hua , Wang Chien-Ying , Hsiao Chen-Yuan , Chiang Ching-Shu , Chou Shu-Cheng , Chen Jui-Yu , Tsai Pei-Jiun
Published: January 2022

Objective

Acute pancreatitis can usually recover after conservative treatment. Five to 10 percent of acute pancreatitis may proceed into peripancreatic fluid collection and necrosis development, called necrotizing pancreatitis (NP), which has a high mortality rate. If it is accompanied by the occurrence of abdominal compartment syndrome (ACS) and does not respond to medical therapy, surgical intervention is indicated.

Methods

We analyzed our experience of surgical intervention strategies for NP patients with medically irreversible ACS from January 1, 2004, to December 31, 2018.

Results

Of the 47 NP patients with ACS, mean Ranson score was 6.5, mean Acute Physiology and Chronic Health Evaluation II score was 22.2, and Modified computed tomography severity index score was all 8 or greater. The mean total postoperative hospital length of stay was 80.2 days, of which the mean intensive care unit length of stay was 16.6 days. The overall complication rate was 31.9%. The mortality rate was 8.5%. Among the 47 patients, only fungemia was significantly associated with mortality incidence.

Conclusions

The combination of multiple drainage tube placement, feeding jejunostomy, and ileostomy at the same time were effective surgical intervention strategies for NP patients with ACS, which brought a lower mortality rate.
Phase II Trial of Bevacizumab Monotherapy in Pancreatic Neuroendocrine Tumors
Authors: Zhu Mojun , Costello Brian A. , Yin Jun , Pettinger Adam M. , Strosberg Jonathan R. , Erlichman Charles , Hobday Timothy J.
Published: January 2022

Objectives

Systemic therapies for pancreatic neuroendocrine tumors (PNETs) are limited. The combination of bevacizumab and temsirolimus showed significant antitumor activity, but the single-agent activity of bevacizumab was unknown. We conducted a single-arm, phase II trial to evaluate the efficacy of bevacizumab in PNETs.

Methods

Patients with progressive disease by the Response Evaluation Criteria in Solid Tumors version 1.1 within 7 months of enrollment were eligible for bevacizumab 10 mg/kg every 2 weeks. Adverse events were assessed according to the Common Terminology Criteria for Adverse Events version 3.0. The primary end point was response rate (RR).

Results

Twenty-four patients were enrolled and followed up for a median duration of 36.1 months. Confirmed RR was 12.5%; 75.0% of patients had stable disease at 6 months. Median progression-free survival was 18.0 months; median overall survival was not reached. Common grade 3 adverse events were hypertension (45.8%) and proteinuria (8.3%). No grade 4 adverse events were observed.

Conclusions

Bevacizumab demonstrated promising antitumor activity in progressive PNETs comparable to standard targeted therapy. Although this study failed to reject the null hypothesis (RR, 10%), bevacizumab seems a reasonable monotherapy and a potential component of combination therapies given clinical activity and low rates of adverse events.
Targeting of Smad7 in Mesenchymal Cells Does Not Exacerbate Fibrosis During Experimental Chronic Pancreatitis
Authors: Li Xuan , Nania Salvatore , Kleiter Ingo , Löhr J.-Matthias , Heuchel Rainer L.
Published: January 2022

Objectives

Transforming growth factor-β (TGF-β)–mediated accumulation of extracellular matrix proteins such as collagen I is a common feature of fibrosis. Pancreatic stellate cells play an integral role in the pathogenesis of pancreatitis, and their profibrotic ability is mainly mediated by TGF-β signaling. To specifically address the role of fibrogenic cells in experimental pancreatic fibrosis, we deleted Smad7, the main feedback inhibitor of TGF-β signaling in this cell type in mice.

Methods

A mouse strain harboring a conditional knockout allele of Smad7 (Smad7fl/fl
) with the tamoxifen-inducible inducible Col1a2-CreERT
allele was generated and compared with wild-type mice challenged with the cerulein-based model of chronic pancreatitis.

Results

Pancreatic stellate cells lacking Smad7 had significantly increased collagen I and fibronectin production and showed a higher activation level in vitro. Surprisingly, the fibrotic index in the pancreata of treated conditional knockout mice was only slightly increased, without statistical significance. Except for fibronectin, the expression of different extracellular matrix proteins and the numbers of fibroblasts and inflammatory cells were similar between Smad7-mutant and control mice.

Conclusions

There was no clear evidence that the lack of Smad7 in pancreatic stellate cells plays a major role in experimental pancreatitis, at least in the mouse model investigated here.
Hypophosphatemia Is More Common and Is Prognostic of Poorer Outcomes in Severe Alcoholic Pancreatitis
Authors: Wagner Jason , Hernandez-Blanco Yllen , Yu Abraham , Garcia-Rodriguez Victor , Mohajir Wasay , Goodman Colin , Farooq Ahmad
Published: January 2022

Objectives

The aim of this study was to determine if hypophosphatemia is more common in patients with severe alcohol-induced acute pancreatitis (AAP).

Methods

This is a retrospective, single institution, cohort study that analyzed 147 patients admitted to the hospital for AAP. Multivariate logistic regression was used to determine if hypophosphatemia would be related to clinical outcomes of disease severity.

Results

Hypophosphatemia was more common in patients with severe AAP at admission; in addition, all patients with severe AAP (100%) eventually developed hypophosphatemia during admission, relative to those with mild (43%) and moderately severe (54%) AAP. The magnitude of the lowest phosphate measurement obtained during admission was lower in patients with severe AAP (mean, 1.5 mg/dL, standard deviation [SD], 0.5 mg/dL) relative to those with mild (mean, 2.6 mg/dL; SD, 0.9 mg/dL) and moderately severe (mean, 2.3 mg/dL; SD, 0.9 mg/dL) AAP (P < 0.001). Finally, patients who developed hypophosphatemia during admission were more likely to require intensive care unit admission (P < 0.001), vasopressors (P = 0.01), or intubation (P = 0.003).

Conclusions

Hypophosphatemia is more common and of greater magnitude in patients admitted to the hospital with severe AAP. In addition, patients with severe AAP who develop hypophosphatemia during admission are more likely to have poorer clinical outcomes.
Superficial Circumflex Iliac Artery Perforator Flap in Advanced Head and Neck Reconstruction: From Simple to Its Chimeric Patterns and Clinical Experience with 22 Cases
Authors: Scaglioni Mario F. , Meroni Matteo , Fritsche Elmar , Rajan Gunesh
Published: January 2022

Background:

Head and neck tissue defects after ablative head and neck surgery often require complex and composite reconstructions. The superficial circumflex iliac artery perforator (SCIP) flap is an extremely versatile perforator-based flap with minimal donor-site morbidity. The authors present their experience with both simple and chimeric SCIP flap reconstructions for complex defects in various head and neck regions.

Methods:

Twenty-two patients undergoing ablative head and neck surgery for oncologic abnormalities were treated by means of a SCIP flap reconstruction. Patients’ mean age was 62 years; 21 were men and one was a woman. Seventeen flaps were simple and five were chimeric reconstruction patterns. Indocyanine green perfusion imaging was performed in all cases.

Results:

Twenty-one of 22 patients (95.5 percent) were successfully treated with good aesthetic and functional results. Two patients (9 percent) showed minor donor-site complications that were managed conservatively. The mean follow-up period was 5.3 months (range, 2 to 8 months).

Conclusions:

This case series demonstrates the reliability and versatility of the SCIP flap for head and neck reconstruction. The chimeric options combined with bone, double-skin paddle, and muscle offer a broad variety of functional reconstructive solutions for complex head and neck surgery. Intraoperative indocyanine green perfusion examinations are a valuable tool to assess and ascertain proper inset, vitality, and postanastomosis vessel patency in these complex microvascular flap reconstructions. 

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Prevalence and Risk Factors of Urinary Incontinence Among Elderly Adults in Rural China
Authors: Luo Yan , Zou Ping , Wang Kai , Li Xiaomei , Wang Jing
Published: January 2022

PURPOSE:

The purpose of this study was to explore the prevalence of urinary incontinence (UI) and several subtypes: (stress, urge, and mixed UI) and the influence of multiple factors on the likelihood of UI.

DESIGN:

Epidemiological study based on cross-sectional data collection.

SUBJECTS AND SETTING:

The sample comprised 1279 inhabitants 65 years and older residing in 10 villages randomly selected from the Shanxi province, located in North China.

METHODS:

The presence and types of UI were assessed using the International Consultation of Incontinence Questionnaire-Short Form. Sociodemographic parameters were also recorded, along with data on lifestyle, bowel function, and medical conditions. The Activity of Daily Living Scale and Mini-Mental State Examination instruments were used to evaluate physical and cognitive functions, respectively. A multivariate logistic regression model with the backward method was employed to identify factors associated with UI.

RESULTS:

The prevalence of any UI among the rural Chinese elderly 65 years and older was 46.8%, with a female predominance (56.3% in females vs 35.0% in males). The most common incontinence subtype in women was mixed UI (n = 170, 24.0%), followed by stress UI (n = 131, 18.5%) and urge UI (n = 97, 13.7%). The most prevalent form of UI in males was urge UI (n = 190, 33.2%), followed by stress UI (n = 5, 0.9%) and mixed UI (n = 5, 0.9%). Less than one quarter of respondents (17%, n = 102) of participants with UI had consulted a doctor. Multivariate analysis found that poorer physical function, poor quality of sleep, and fecal incontinence were common factors associated with UI in both women and men. In women, higher body mass index and constipation were also independent correlates, as were poor vision and heart disease in men. Poorer physical function was associated with all UI subtypes. For female stress UI, poorer cognitive status, tea drinking, and hypertension also emerged as independent risk factors. Heart disease was an independent risk factor in both female and male urge UI; as was consumption of a non-plant-based diet for female mixed and urge UI; nonfarmer and traumatic brain injury for female urge UI; and poor vision and fecal incontinence in male urge UI.

CONCLUSIONS:

Chinese rural citizens showed a high UI prevalence, but only a small proportion had consulted a health care provider. Physical function decline was the most important contributor to UI among participants. Individualized intervention programs targeting modifiable risk factors among high-risk populations should be developed.
Factors Affecting Medication Adherence Among patient with Schizophrenia: A Literature Review
Authors: Rohmi Faizatur , Rumambo Pandin Moses Glorino
Published: January 2022

This review aimed to summarize empirical evidence concerning to the factors relating to medication adherence among patients with schizophrenia. A comprehensive search was implemented to recruit articles which met the present eligibility criteria. Twenty articles were included, all of which were quantitative studies. Greater awareness of illness (insight), previous history of medication adherence, positive attitude toward medication, types of atypical antipsychotics, less severe psychotic symptoms, and social support, self-efficacy, general health status, gender men, lower socioeconomic status, living alone, length of illness, drug abuse, education level, severity of illness for example being in the acute phase, participating in mental health services, health facilities, marital status, receiving monotherapy were identified as factors of medication adherence. Implications to clinical practice include providing psychoeducation to patients and family by increasing their knowledge about illness and medication.
A new method for the sampling and preservation of placental specimens in low-resource settings for the identification of P. falciparum and analysis of nucleic acids
Authors: Potoczak Patrick S. , Strassmann Beverly I. , Vincenz Claudius
Published: January 2022

Collection, preservation, and shipment of histological specimens in low-resource settings is challenging. We present a novel method that achieved excellent preservation of placental specimens from rural Mali by using formalin fixation, ethanol dehydration, and long-term storage in a solar-powered freezer. Sample preservation success was 92%, permitting evaluation of current and past malaria infection, anemia, placental maturity, and inflammation. Using RNAscope® hybridization we were able to visualize cell-specific gene expression patterns in the formalin-fixed paraffin-embedded (FFPE) specimens. Additionally, our method entailed mirrored sampling from the two cut faces of a cotyledon, one for the FFPE workflows and the other for storage in RNAlater™ and RNA-seq.
Second Climate Survey of Biomedical PhD Students in the Time of Covid
Authors: Ramadoss Deepti , Horn John P.
Published: January 2022

In July 2021, sixteen months into the Covid-19 pandemic, the institutional climate for PhD training in the School of Medicine was assessed for a second time. This survey of graduate students occurred 1 year after initial surveys of graduate students and training faculty in July 2020. The 2021 survey was completed by 99 PhD students in 11 PhD-granting programs. To allow comparisons between years, most of the 2021 questions were repeated with only minor edits. A few items were added to assess impacts of school-wide town hall meetings, a new PhD career club program, and enlarged mental health services. Several themes emerged. Students remain extremely concerned about the pandemic’s impact upon their training and long-term career prospects. They worry specifically about pandemic related reductions in research productivity and networking opportunities. Many students successfully adapted to laboratory research under pandemic restrictions but suffer from the continuing lack of social interaction even after in-person work hours increased. Symptoms of anxiety and/or depression persist amongst 46% of the students, as compared to 51% in 2020. Nearly 80% of students continue to report strong satisfaction with mentoring relationships with their dissertation advisors, but to lesser extents with programs (66%), departments or centers (71%), the School of Medicine (32%) and the University (49%). Students (26%) express interest in the Ombuds office that was announced in late 2021. Some students wrote that the medical school could do a better job in embracing diversity and inclusion and in mentor training, and many stated that town hall meetings do not serve them well. Coping mechanisms shared by some students demonstrate impressive resilience. These results present a mixed picture. While aspects of biomedical PhD training have begun to recover as the pandemic continues, long-term consequences of the disruption raise challenges that must be addressed by efforts to restore and improve the learning environment required for 21st century research education.
Differential remodelling in small and large murine airways revealed by novel whole lung airway analysis
Authors: Tatler Amanda L , Philp Christopher J , Hill Michael R , Cox Sam , Bullock Andrew , Habgood Anthony , John Alison , Middlewick Robert , Stephenson Katherine E , Goodwin Amanda T , Billington Charlotte K , O’Dea Reuben D , Brook Bindi S , Johnson Simon R
Published: January 2022

Airway remodelling occurs in chronic asthma leading to increased airway smooth muscle (ASM) mass and extra-cellular matrix (ECM) deposition. Whilst extensively studied in murine airways; studies report only selected larger airways at one time point meaning the spatial distribution and resolution of remodelling are poorly understood. Here we use a new method allowing comprehensive assessment of the spatial and temporal changes in ASM, ECM and epithelium in large numbers of murine airways after allergen challenge. Using image processing to analyse 20-50 airways from a whole lung section revealed increases in ASM and ECM after allergen challenge were greater in small and large rather than intermediate airways. ASM predominantly accumulated adjacent to the basement membrane whereas ECM was distributed across the airway wall. Epithelial hyperplasia was most marked in small and intermediate airways. Post challenge, ASM changes resolved over seven days whereas ECM and epithelial changes persisted. The new method suggests large and small airways remodel differently and the long-term consequences of airway inflammation may depend more on ECM and epithelial changes than ASM. The method reduces the number of animals needed, reveals important spatial differences in remodelling and could set new analysis standards for murine asthma models.
scSampler: fast diversity-preserving subsampling of large-scale single-cell transcriptomic data
Authors: Song Dongyuan , Xi Nan Miles , Li Jingyi Jessica , Wang Lin
Published: January 2022

The number of cells measured in single-cell transcriptomic data has grown fast in recent years. For such large-scale data, subsampling is a powerful and often necessary tool for exploratory data analysis. However, the easiest random subsampling is not ideal from the perspective of preserving rare cell types. Therefore, diversity-preserving subsampling is required for fast exploration of cell types in a large-scale dataset. Here we propose scSampler, an algorithm for fast diversity-preserving subsampling of single-cell transcriptomic data. Using simulated and real data, we show that scSampler consistently outperforms existing subsam-pling methods in terms of both the computational time and the Hausdorff distance between the full and subsampled datasets.

Availability

scSampler is implemented in Python and is published under the MIT source license. It can be installed by pip install scsampler and used with the Scanpy pipline. The code is available on GitHub: https://github.com/SONGDONGYUAN1994/scsampler.

Contact

linwang@gwu.edu; jli@stat.ucla.edu
Longitudinal monitoring of disease burden and response using ctDNA from dried blood spots in xenograft models
Authors: Sauer Carolin M , Heider Katrin , Belic Jelena , Boyle Samantha E , Hall James A , Couturier Dominique-Laurent , An Angela , Vijayaraghavan Aadhitthya , Reinius Marika AV , Hosking Karen , Vias Maria , Rosenfeld Nitzan , Brenton James D
Published: January 2022

Whole genome sequencing (WGS) of circulating tumour DNA (ctDNA) is now a clinically important biomarker for predicting therapy response, disease burden and disease progression. However, the translation of ctDNA monitoring into vital pre-clinical PDX models has not been possible owing to low circulating blood volumes in small rodents. Here, we describe the longitudinal detection and monitoring of ctDNA from minute volumes of blood in PDX mice. We developed a xenograft Tumour Fraction (xTF) metric using shallow WGS of dried blood spots (DBS), and demonstrate its application to quantify disease burden, monitor treatment response and predict disease outcome in a pre-clinical study of PDX mice. Further, we show how our DBS-based ctDNA assay can be used to detect gene-specific copy number changes and examine the copy number landscape over time. Use of sequential DBS ctDNA assays will transform future trial designs in both mice and patients.
Differential Impact of Doxorubicin Dose on Cell Death and Autophagy Pathways during Acute Cardiotoxicity
Authors: Kawalec Philip , Martens Matthew D. , Field Jared T. , Mughal Wajihah , Caymo Andrei Miguel , Chapman Donald , Xiang Bo , Ghavami Saeid , Dolinsky Vernon W. , Gordon Joseph W.
Published: January 2022

Doxorubicin (DOX) is an effective anthracycline used in chemotherapeutic regimens for a variety of haematological and solid tumors. However, its utility remains limited by its well-described, but poorly understood cardiotoxicity. Despite numerous studies describing various forms of regulated cell death and their involvement in DOX-mediated cardiotoxicity, the predominate form of cell death remains unclear. Part of this inconsistency lies in a lack of standardization of in vivo and in vitro model design. To this end, the objective of this study was to characterize acute low- and high-dose DOX exposure on cardiac structure and function in C57BL/6N mice, and evaluate regulated cell death pathways and autophagy both in vivo and in cardiomyocyte culture models. Acute low-dose DOX had little impact on cardiac structure or function; however, acute high-dose DOX elicited substantial cardiac necrosis resulting in diminished cardiac mass and volume, with a corresponding reduced cardiac output, and without impacting ejection fraction or fibrosis. Low-dose DOX consistently activated caspase-signaling with evidence of mitochondrial permeability transition. However, acute high-dose DOX had only modest impact on common necrotic signaling pathways, but instead led to an inhibition in autophagic flux. Intriguingly, when autophagy was inhibited in cultured cardiomyoblasts, DOX-induced necrosis was enhanced. Collectively, these observations implicate inhibition of autophagy flux as an important component of the acute necrotic response to DOX, but also suggest that acute high-dose DOX exposure does not recapitulate the disease phenotype observed in human cardiotoxicity.
The coupling between healthspan and lifespan in Caenorhabditis depends on complex interactions between compound intervention and genetic background
Authors: Banse Stephen A. , Jackson E. Grace , Sedore Christine A. , Onken Brian , Hall David , Coleman-Hulbert Anna , Huynh Phu , Garrett Theo , Johnson Erik , Harinath Girish , Inman Delaney , Guo Suzhen , Morshead Mackenzie , Xue Jian , Falkowski Ron , Chen Esteban , Herrera Christopher , Kirsch Allie J , Perez Viviana I. , Guo Max , Lithgow Gordon J. , Driscoll Monica , Phillips Patrick C.
Published: January 2022

Aging is characterized by declining health that results in decreased neuromuscular function and cellular resilience. The relationship between lifespan and health, and the influence of genetic background on that relationship, has important implications in the development of anti-aging interventions. Here we combined survival under thermal and oxidative stress with swimming performance, to evaluate health effects across a nematode genetic diversity panel for three compounds previously studied in the Caenorhabditis Intervention Testing Program – NP1, propyl gallate, and resveratrol. We show that oxidative stress resistance and thermotolerance vary with compound intervention, genetic background, and age. The effects of tested compounds on swimming locomotion, in contrast, are largely species-specific. Additionally, thermotolerance, but not oxidative stress or swimming ability, correlates with lifespan. Our results demonstrate the importance of assessing health and lifespan across genetic backgrounds in the effort to identify reproducible aging interventions.
De novoanalysis of bulk RNA-seq data at spatially resolved single-cell resolution
Authors: Liao Jie , Qian Jingyang , Fang Yin , Chen Zhuo , Zhuang Xiang , Zhang Ningyu , Shao Xin , Hu Yining , Yang Penghui , Cheng Junyun , Hu Yang , Yu Lingqi , Yang Haihong , Zhang Jinlu , Lu Xiaoyan , Shao Li , Wu Dan , Gao Yue , Chen Huajun , Fan Xiaohui
Published: January 2022

Uncovering the tissue molecular architecture at single-cell resolution could help better understand organisms’ biological and pathological processes. However, bulk RNA-seq can only measure gene expression in cell mixtures, without revealing the transcriptional heterogeneity and spatial patterns of single cells. Herein, we introduce Bulk2Space (https://github.com/ZJUFanLab/bulk2space), a deep learning framework-based spatial deconvolution algorithm that can simultaneously disclose the spatial and cellular heterogeneity of bulk RNA-seq data using existing single-cell and spatial transcriptomics references. The use of bulk transcriptomics to validate Bulk2Space unveils, in particular, the spatial variance of immune cells in different tumor regions, the molecular and spatial heterogeneity of tissues during inflammation-induced tumorigenesis, and spatial patterns of novel genes in different cell types. Moreover, Bulk2Space is utilized to perform spatial deconvolution analysis on bulk transcriptome data from two different mouse brain regions derived from our in-house developed sequencing approach termed Spatial-seq. We have not only reconstructed the hierarchical structure of the mouse isocortex but also further annotated cell types that were not identified by original methods in the mouse hypothalamus.
Yeast biopanning for detecting antibody binding to site-specific phosphorylations in tau
Authors: Arbaciauskaite Monika , Pirhanov Azady , Lei Yu , Cho Yong Ku
Published: January 2022

The detection of phosphorylated tau (p-tau) levels in clinical samples is of extreme importance for the detection of Alzheimer’s Disease (AD) as well as other neurodegenerative diseases. Recent reports show that detecting low levels of p-tau in plasma can be used as a reliable biomarker for detecting AD prior to the onset of memory loss. The ability to detect such low levels of p-tau is dependent on antibodies specific to the post translationally modified protein. However, the need for reliable phospho-site specific antibodies persists due to a lack of approaches for identifying monoclonal antibodies and characterizing non-specific binding. Here, we report a novel approach using the principles of yeast biopanning to create a robust platform that uses synthetic peptides as target antigens. Using peptides as antigens enables screening antibodies against defined post-translational modification sites, particularly for targeting intrinsically disordered proteins such as the human tau protein. To readily assess yeast binding and distinguish non-specific binding, we developed bi-directional expression vectors that allow antibody fragment surface display and intracellular fluorescent protein expression. We show that our platform can specifically and robustly detect a specific site within the p-tau target peptide when compared against non-phosphorylated controls. By improving biopanning parameters, we enabled phospho-specific capture of yeast cells displaying single-chain variable region fragments (scFvs) against p-tau with a wide range of affinities (KD = 0.2 to 60 nM). These results demonstrate that yeast biopanning can robustly capture yeast cells based on phospho-site specific antibody binding, opening doors for facile identification of high-quality monoclonal antibodies.
Wireless closed-loop smart bandage for chronic wound management and accelerated tissue regeneration
Authors: Jiang Yuanwen , Trotsyuk Artem A. , Niu Simiao , Henn Dominic , Chen Kellen , Shih Chien-Chung , Larson Madelyn R. , Mermin-Bunnell Alana M. , Mittal Smiti , Lai Jian-Cheng , Saberi Aref , Beard Ethan , Jing Serena , Zhong Donglai , Steele Sydney R. , Sun Kefan , Jain Tanish , Zhao Eric , Neimeth Christopher R. , Viana Willian G. , Tang Jing , Sivaraj Dharshan , Padmanabhan Jagannath , Rodrigues Melanie , Perrault David P. , Chattopadhyay Arhana , Maan Zeshaan N. , Leeolou Melissa C. , Bonham Clark A. , Kwon Sun Hyung , Kussie Hudson C. , Fischer Katharina S. , Gurusankar Gurupranav , Liang Kui , Zhang Kailiang , Nag Ronjon , Snyder Michael P. , Januszyk Michael , Gurtner Geoffrey C. , Bao Zhenan
Published: January 2022

Chronic non-healing wounds represent a major source of morbidity for patients and a significant economic burden. Current wound care treatments are generally passive and are unable to adapt to changes in the wound environment in real time. By integrating multimodal sensors and adding stimulators in a bandage, real-time physiological monitoring is possible and provides an opportunity for active intervention into the complex wound environment. Here, we develop a battery-free flexible bioelectronic system consisting of wirelessly powered, closed-loop sensing and stimulation circuits with tissue-interfacing tough conducting hydrogel electrodes for robust signal transduction, on-demand adhesion, and detachment. Using multiple pre-clinical models, we demonstrate the capability of our wound care system to continuously monitor skin impedance and temperature, to trigger directional electrical stimulation. The accelerated wound closure was confirmed to be due to the activation of pro-regenerative genes linked to accelerated wound closure, increased neovascularization, and enhanced dermal recovery.
ISSAAC-seq enables sensitive and flexible multimodal profiling of chromatin accessibility and gene expression in single cells
Authors: Xu Wei , Yang Weilong , Zhang Yunlong , Chen Yawen , Hong Ni , Zhang Qian , Wang Xuefei , Hu Yukun , Song Kun , Jin Wenfei , Chen Xi
Published: January 2022

Joint profiling of chromatin accessibility and gene expression from the same single cell/nucleus provides critical information about cell types in a tissue and cell states during a dynamic process. These emerging multi-omics techniques help the investigation of cell-type resolved gene regulatory mechanisms1–7. However, many methods are currently limited by low sensitivity, low throughput or complex workflow. Here, we developed in situ SHERRY after ATAC-seq (ISSAAC-seq), a highly sensitive and flexible single cell multi-omics method to interrogate chromatin accessibility and gene expression from the same single nucleus. We demonstrated that ISSAAC-seq is sensitive and provides high quality data with orders of magnitude more features than existing methods. Using the joint profiles from over 10,000 nuclei from the mouse cerebral cortex, we uncovered major and rare cell types and cell-type specific regulatory elements and identified heterogeneity at the chromatin level within established cell types defined by gene expression. Finally, we revealed distinct dynamics and relationships of gene expression and chromatin accessibility during an oligodendrocyte maturation trajectory.
Stomatal anatomy, leaf structure and nutrients of tropical rainforest tree species respond to altitude in a coordinated manner in accordance with the leaf economics spectrum
Authors: Weththasinghe Bhagya , Caldera Iroja , Sanjeewani Nimalka , Samarasinghe Dilum , Jayasinghe Himesh , Wijethunga Asanga , De Costa Janendra
Published: January 2022

Understanding taxon level responses of key plant traits to environmental variation across tropical rainforests (TRFs) is important to determine their response to climate change. We used an altitudinal gradient (from 150 to 2100 m above sea level, asl) across TRFs in Sri Lanka to answer the following questions: (a) Does the response to altitude by stomatal traits differ among plant taxa in TRFs?; (b) Are the altitudinal responses of key leaf structural traits (e.g. leaf mass per area, LMA) and major leaf nutrient (nitrogen, N, and phosphorus, P) concentrations linked to the corresponding variation in stomatal traits in a coordinated response across taxa?; (c) How strong is the influence of climatic variation on responses of leaf traits to altitude?. Leaf samples were collected in permanent sampling plots within rainforest reserves at Kanneliya (150 m asl), Sinharaja-Enasalwatta (1050 m), Hakgala (1800 m) and Piduruthalagala (2100 m) from 19 species in three plant genera (Calophyllum, Semecarpus and Syzygium). Stomatal density, guard cell length and epidermal density showed variation among taxa, but did not respond to altitude. Potential conductance index (PCI), a proxy for photosynthetic capacity, decreased with increasing altitude, in a common response across taxa. We found evidence that altitudinal responses of LMA, leaf N and P were linked to stomatal responses in a coordinated manner, where key features were the negative correlations between PCI and LMA and between proxy photosynthetic N- and P-use efficiencies (‘PNUE’ and ‘PPUE’) and LMA. We found strong responses to climatic variation across taxa and altitudes, where PCI, ‘PNUE’ and ‘PPUE’ increased and LMA decreased with increasing temperature, precipitation and solar irradiance. We conclude that stomatal traits of tree species in TRFs form part of a coordinated leaf trait response to environmental change which is in accordance with the leaf economics spectrum.