bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiometabolic health impacts of time-restricted eating: implications for type 2 diabetes, cancer and cardiovascular diseases
Authors: Kirkham Amy A. , Parr Evelyn B. , Kleckner Amber S.
Published: August 2022

Purpose of review

Time-restricted eating (TRE) entails consuming energy intake within a 4- to 10-h window, with the remaining time spent fasting. Although studies have reported health benefits from TRE, little is known about the impact of TRE on common chronic diseases such as type 2 diabetes, cancer and cardiovascular disease. This review summarizes and critically evaluates the most recent TRE research findings relevant to managing and treating these chronic diseases.

Recent findings

Most recent TRE studies have been in populations with overweight/obesity or metabolic syndrome; two have been in populations with diabetes, three in cancer survivors and none in populations with cardiovascular disease. Collectively, these studies showed that participants could adhere to TRE and TRE is well tolerated. These studies also showed preliminary efficacy for improved glucose regulation and insulin sensitivity, a reduction in body fat and blood pressure, reduced cardiovascular risk scores and increased quality of life. More research is required to define the most effective TRE protocol (i.e. length and timing of eating window, intervention duration).

TRE has demonstrated benefits on cardiovascular, metabolic and clinical outcomes relevant to the underlying pathophysiology, but there are limited data on TRE implemented specifically within populations with diabetes, cancer or cardiovascular disease.
Colchicine Poisoning Cases in a Pediatric Intensive Care Unit
Authors: Süzen-Orhan Eda , Botan Edin , Gün Emrah , Özen Hasan , Gurbanov Anar , Balaban Burak , Kahveci Fevzi , Vatansever Göksel , Tekin Deniz , Kendirli Tanıl
Published: August 2022

Objectives

Colchicine intoxication is rare but potentially fatal. The toxic dose of colchicine is not well established; it has been reported that major toxicity starts after doses of 0.5 mg/kg. We aimed to evaluate the demographic, clinical aspects, treatments, and outcome of colchicine toxicity cases in the pediatric intensive care unit (PICU).

Methods

We collected the data of patients aged between 0 and 18 years, admitted to Ankara University Faculty of Medicine PICU for colchicine poisoning (n = 22), from October 1999 to January 2020, retrospectively. Data extracted from the cases included age, sex, chronic condition, time between intake of drug and admission to PICU, source of drug, amount of drug ingested, other drug intake, symptoms, clinical findings, cardiac involvement, laboratory results, time of stay in PICU, treatment, and outcome.

Results

Patients' age ranged from 7 months to 17 years. Median age was 86 months. The most common symptom at time of admission was vomiting, occurring in 13 (59%) of the patients. Two of the patients presented with change in mental status. Time between taking medication and applying to the hospital ranged from half an hour to 4 days. Medication intake of 3 of 22 patients was more than 0.5 mg/kg. One patient whose parents' best estimate of dose ingested was 0.48 mg/kg died because of the development of multiorgan failure. One patient who ingested 0.4 mg/kg of colchicine underwent plasma exchange and recovered without any complications.

Conclusions

Colchicine poisoning has a high risk of mortality, and death can be seen in doses less than a single acute dose of 0.5 mg/kg. These patients need close monitoring because there is always a risk of them to require aggressive support. Prognosis is poor in patients who have rapidly developing hemodynamic failure.
Financial and Safety Impact of Simulation-based Clinical Systems Testing on Pediatric Trauma Center Transitions
Authors: Williams Sacha A. , Fitzpatrick Katie , Chandler Nicole M. , Arnold Jennifer L. , Snyder Christopher W.
Published: August 2022

Introduction:

Simulation offers multiple tools that apply to medical settings, but little is known about the application of simulation to pediatric trauma workflow changes. Our institution recently underwent significant clinical changes in becoming an independent pediatric trauma center. We used a simulation-based clinical systems testing (SbCST) approach to manage change-associated risks. The purpose of this study was to describe our SbCST process, evaluate its impact on patient safety, and estimate financial costs and benefits.

Methods:

SbCST consisted of the following steps: (1) change-based needs assessment, in which stakeholders developed relevant simulation scenarios; (2) scenario implementation; and (3) postsimulation failure mode and effects analysis (FMEA) to identify latent safety threats (LSTs). LSTs were prioritized for mitigation based on the expected probability and severity of adverse event occurrences. We calculated the costs associated with the simulation process. We conservatively estimated SbCST cost savings using 3 approaches: (1) FMEA-based avoidance of adverse events; (2) avoidance of trauma readmissions; and (3) avoidance of medical liability lawsuits.

Results:

We implemented 2 simulation scenarios prechange. FMEA revealed 49 LSTs, of which 9 were highest priority (catastrophic severity and high likelihood of occurrence). These were prioritized and mitigated using the hospital’s quality/safety framework. Cost-benefit analysis based on FMEA event avoidance demonstrated net cost savings to the institution ranging from $52,000−227,000 over the 3-month postchange period. Readmission-based and liability-based estimates also produced favorable results.

Conclusions:

The SbCST approach identified multiple high-impact safety risks and financially benefited the institution in managing significant pediatric trauma clinical process changes.
Vasopressor-resistant hypotension, combination vasopressor therapy, and shock phenotypes in critically ill adults with vasodilatory shock
Authors: Priyanka Priyanka , Chang Chung-Chou H. , Chawla Lakhmir S. , Kellum John A. , Clermont Gilles , Murugan Raghavan
Published: August 2022

Objective

To examine the risk factors, resource utilization and 1-year mortality associated with vasopressor-resistant hypotension (VRH) compared with vasopressor-sensitive hypotension (VSH) among critically ill adults with vasodilatory shock. We also examined whether combination vasopressor therapy and patient phenotype were associated with mortality.

Design

Retrospective cohort study.

Setting

Eight medical-surgical ICUs at the University of Pittsburgh Medical Center, Pittsburgh, PA.

Patients

Critically ill patients with vasodilatory shock admitted between July 2000 through October 2008.

Interventions

None.

Measurements & Main Results

VRH was defined as those requiring >0.2 mcg/kg/minute of norepinephrine equivalent dose of vasopressor consecutively for more than 6 hours and VSH was defined as patients requiring ≤0.2 mcg/kg/min to maintain mean arterial pressure between 55-70 mmHg after adequate fluid resuscitation. Of 5,313 patients with vasodilatory shock, 1,291 (24.3%) patients developed VRH. Compared with VSH, VRH was associated with increased risk of acute kidney injury (72.7% vs. 65.0%; P < 0.001), use of kidney replacement therapy (26.0% vs. 11.0%; P < 0.001), longer median (IQR) ICU length of stay (10 [IQR, 4.0-20.0] vs. 6 [IQR, 3.0-13.0] days; P < 0.001), and increased 1 year mortality (64.7% vs. 34.8%; P < 0.001). VRH was associated with increased odds of risk-adjusted mortality (adjusted odds ratio, [aOR], 2.93, 95% CI, 2.52-3.40; P < 0.001). When compared with monotherapy, combination vasopressor therapy with two (aOR, 0.91, 95%CI, 0.78 -1.06) and three or more vasopressors were not associated with lower mortality (aOR, 0.93, 95%CI, 0.68-1.27). Using a finite mixture model, we identified four unique phenotypes of patient clusters that differed with respect to demographics, severity of illness, processes of care, vasopressor use and outcomes.

Conclusions

Among critically ill patients with vasodilatory shock, VRH compared with VSH, is associated with increased resource utilization and long-term risk of death. However, combination vasopressor therapy was not associated with lower risk of death. We identified four unique phenotypes of patient clusters that requires further validation.
INTESTINAL DAMAGE AND IMMUNE RESPONSE AFTER EXPERIMENTAL BLUNT ABDOMINAL TRAUMA
Authors: Haussner Felix , Maitz Alexander , Rasche Volker , Hoffmann Andrea , Braumüller Sonja , Lupu Ludmila , Ignatius Anita , Neff Thomas A. , Palmer Annette , Huber-Lang Markus
Published: August 2022

Abdominal trauma (AT) is of major global importance, particularly because the civil, terroristic, and military traumatic potential of blast injuries has increased. The consequences of blunt abdominal injuries are highly variable and frequently underestimated or even overlooked. However, the underlying path mechanisms and subsequent innate immune response remain poorly understood. Therefore, we investigated the spatiotemporal local and systemic effects of a standardized blast-induced blunt AT on the intestine and innate immune response. In an established AT model, 66 male C57Bl6 mice were anesthetized and exposed to either a single blast wave centered on the epigastrium or control treatment (sham). At 2, 6, or 24 hours after trauma induction, animals were sacrificed. In 16 of 44 (36%) AT animals, one or more macroscopically visible injuries of the intestine were observed. Epithelial damage was detected by histological analysis of jejunum and ileum tissue samples, quantified by the Chiu score and by increased plasma concentrations of the intestinal fatty acid–binding protein, an enterocyte damage marker. Moreover, in the early posttraumatic period, elevated syndecan-1, claudin-5, and mucin-2 plasma levels also indicated alterations in the gut-blood barrier. Increased levels of pro-inflammatory cytokines such as TNF and macrophage inflammatory protein 2 in tissue homogenates and plasma indicate a systemic immune activation after blunt AT. In conclusion, we detected early morphological intestinal damage associated with high, early detectable intestinal fatty acid–binding protein plasma levels, and a considerable time- and dose-dependent impairment of the gut-blood barrier in a newly established mouse model of blunt AT. It appears to be a sufficient model for further studies of the intestinal immunopathophysiological consequences of AT and the evaluation of novel therapeutic approaches.
Persistence and Recurrence of Hypercalcemia After Parathyroidectomy Over 5 Decades (1965–2010) in a Community-based Cohort
Authors: Szabo Yamashita Thomas , Mirande Maxwell , Huang Chieh-Ting , Kearns Ann , Fyffe-Freil Ria , Singh Ravinder , Foster Trenton , Thompson Geoffrey , Lyden Melanie , McKenzie Travis , Wermers Robert A. , Dy Benzon
Published: August 2022

Background:

There is limited long-term follow-up of patients undergoing parathyroidectomy. Recurrence is described as 4% to 10%. This study evaluated persistence and recurrence of hypercalcemia in primary hyperparathyroidism after parathyroidectomy.

Methods:

Single-institution retrospective (1965–2010) population-based cohort from Olmsted County (MN) of patients undergoing surgery for primary hyperparathyroidism. Patients’ demographic data, preoperative and postoperative laboratory values, clinical characteristics, surgical treatment, and follow-up were noted.

Results:

A total of 345 patients were identified, 75.7% female, and median age 58.4 years [interquartile range (IQR): 17.6]. In all, 68% of patients were asymptomatic and the most common symptoms were musculoskeletal complaints (28.4%) and nephrolithiasis (25.6%). Preoperative median serum calcium was 11 mg/dL (IQR: 10.8–11.4 mg/dL), and median parathyroid hormone was 90 pg/mL (IQR: 61–169 pg/dL). Bilateral cervical exploration was performed in 38% and single gland resection in 79% of cases. Median postoperative serum calcium was 9.2 mg/dL (IQR: 5.5–11.3). Nine percent of patients presented persistence of hypercalcemia, and recurrence was found in 14% of patients. Highest postoperative median serum calcium was 10 mg/dL (IQR: 6–12.4), and median number of postoperative calcium measurements was 10 (IQR: 0–102). Postoperative hypercalcemia was identified in 37% of patient. Fifty-three percent were attributed to secondary causes, most commonly medications, 22%. Three percent of patients required treatment for postoperative hypercalcemia. Median time to recurrence and death were 12.2 and 16.7 years, respectively.

Conclusion:

Recurrent hypercalcemia after successful parathyroidectomy is higher than previously reported. Most cases are transient and often associated to other factors with only the minority requiring treatment. Long-term follow-up of serum calcium should be considered in patients after successful parathyroidectomy.
Time-varying Comparison of All-cause Mortality After Liver Transplantation Between Recipients With and Without Hepatocellular Carcinoma: A Population-based Cohort Study Using the United Kingdom Liver Transplant Registry
Authors: Sehjal Jyoti , Sharples Linda D. , Keogh Ruth H. , Walker Kate , Prachalias Andreas , Heaton Nigel , Ivanics Tommy , van der Meulen Jan , Wallace David
Published: August 2022

Background.

Accurately identifying time-varying differences in the hazard of all-cause mortality after liver transplantation (LT) between recipients with and without hepatocellular carcinoma (HCC) may inform patient selection and organ allocation policies as well as post-LT surveillance protocols.

Methods.

A UK population-based study was carried out using 9586 LT recipients. The time-varying association between HCC and post-LT all-cause mortality was estimated using an adjusted flexible parametric model (FPM) and expressed as hazard ratios (HRs). Differences in this association by transplant year were then investigated. Non–cancer-specific mortality was compared between HCC and non-HCC recipients using an adjusted subdistribution hazard model.

Results.

The HR comparing HCC recipients with non-HCC recipients was below one immediately after LT (1-mo HR = 0.76; 95% confidence interval [CI], 0.59-0.99;P= 0.044). The HR then increased sharply to a maximum at 1.3 y (HR = 2.07; 95% CI, 1.70-2.52;P< 0.001) before decreasing. The hazard of death was significantly higher in HCC recipients than in non-HCC recipients between 4 mo and 7.4 y post-LT. There were no notable differences in the association between HCC and the post-LT hazard of death by transplant year. The estimated non–cancer-specific subdistribution HR for HCC was 0.93 (95% CI, 0.80-1.09;P= 0.390) and not found to vary over time.

Conclusions.

FPMs can provide a more precise comparison of post-LT hazards of mortality between HCC and non-HCC patients. The results provide further evidence that some HCC patients have extra-hepatic spread at the time of LT, which has implications for optimal post-LT surveillance protocols.
Streptomyces plumbidurans sp. nov., a Pb2+-tolerant actinomycete
Authors: Jiao Yu , Fan Bing-Jun , Cao Yan-Ru , Zhu Guo-Xing , Wu Ya-Jie , Zhang Yue , Hou Xiu-Li , He Jiang-Bo , Liang Lian-Ming
Published: August 2022

A novel actinobacterium, designated KC 17012T, was isolated from lead zinc tailings collected from Lanping, Yunnan, PR China. Comparative 16S rRNA gene sequencing showed that KC 17012T belonged to the genus

Streptomyces

and was most closely related to the type strains of

Streptomyces neyagawaensis

(98.34%),

Streptomyces panaciradicis

(98.34%) and

Streptomyces heilongjiangensis

(98.27%). Phylogenetic tree analysis revealed strain KC 17012T formed a distinct clade. The genome size was 8.64 Mbp with a DNA G+C content of 70.8%. Digital DNA–DNA hybridization and average nucleotide identity values between the genome sequence of strain KC 17012T and those of

S. neyagawaensis

JCM 4796T (25.3 and 81.5 %) and

S. panaciradicis

NBRC 109811T (30.1 and 85.7 %) were below the thresholds of 70 and 96% for prokaryotic conspecific assignation. The strain formed long straight aerial hyphae which generated regular short rod spores with spiny surfaces. Growth occurred at 10–45 °C, pH 6–8 and with 0–9 % NaCl (w/v). Strain KC 17012T contained ll-diaminopimelic acid and the major whole-cell hydrolysates included glucose, mannose and ribose. The menaquinones were MK-9(H4), MK-9(H6) and MK-9(H8). The major cellular fatty acids were iso-C15 : 0, anteiso-C15 : 0, iso-C16 : 0 and anteiso-C17 : 0. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, one unidentified lipid and one unidentified phospholipid. On the basis of the results of a polyphasic taxonomic study, it is concluded that KC 17012T represents a novel species of the genus

Streptomyces

, for which the name Streptomyces plumbidurans sp. nov., is proposed. The type strain is KC 17012T (CGMCC 4.7704T=JCM 35204T).
Perspectives of pharmacy employees on an inappropriate use of antimicrobials in Kathmandu, Nepal
Authors: Shrestha Nistha , Manandhar Sulochana , Maharjan Nhukesh , Twati Devina , Dongol Sabina , Basnyat Buddha , Baker Stephen , Karkey Abhilasha
Published: August 2022

Background

Unregulated antimicrobial use is common in both hospital and community settings of low- and middle-income countries (LMICs). However, discrete data regarding the use/misuse of antimicrobials at pharmacies in LMICs are limited. This study was conducted to understand the knowledge, attitude, and practice of pharmacy employees on antimicrobial dispensing in Nepal.

Methods

We conducted a cross-sectional survey using a structured questionnaire on 801 pharmacy employees working in community and hospital pharmacies located in Lalitpur metropolitan city (LMC) of Kathmandu, Nepal between April 2017 and March 2019.

Results

Not all respondents replied to all questions asked. A majority (92%, 738/801) of respondents agreed that the demand for non-prescription antimicrobials was common. Sixty nine percent (437/635) of participants responded that they would ask of prescription before dispensing. Suspected respiratory tract infection was the most common reason demanding for non-prescription antimicrobials, identified by 68% (535/792) of respondents. Azithromycin was the most commonly prescribed and sold antimicrobials, as reported by 46%, (361/787) and 48% (377/779) of participants respectively. A majority (87%; 696/800) of respondents agreed on antimicrobial resistance (AMR) to be a global public health threat; 54% (429/796) perceived antimicrobial misuse to be an important driver of AMR, while only 39% (315/801) replied that judicious dispensing of antimicrobials can help curb AMR.

Conclusion

Our study revealed that the unfounded dispensing and use of antimicrobials is prevalent among pharmacies in Kathmandu, Nepal. This overreliance on antimicrobials, notably azithromycin, may escalated the burden of AMR. We identified several drivers of inappropriate antimicrobial dispensing practice in pharmacies, which will aid public health authorities in addressing these issues. Further studies considering the role of other stakeholders, such as physicians, veterinarians, general public, and policy makers are required to obtain a more holistic perspectives on the practices of antimicrobial use so to curb the extant AMR crisis.
Lipid metabolism dysfunction following symbiont elimination is linked to altered Kennedy pathway homeostasis
Authors: Attardo Geoffrey M. , Benoit Joshua B. , Michalkova Veronika , Kondragunta Alekhya , Baumann Aaron A. , Weiss Brian L. , Malacrida Anna , Scolari Francesca , Aksoy Serap
Published: August 2022

Lipid metabolism is critical for insect reproduction, especially for species that invest heavily into early developmental stages of their offspring. The role of symbiotic bacteria during this process is unknown but likely essential, especially in the case of obligate microbes that fulfill key biological functions in the host. Using a combined lipidomics, functional genomics and biochemical strategy, we examined the role of lipid metabolism in the interaction between the viviparous tsetse fly (Glossina morsitans morsitans) and its obligate endosymbiotic bacteria (Wigglesworthia glossinidia) during tsetse pregnancy. We observed increasedCTP:phosphocholine cytidylyltransferase(cct1) expression during pregnancy. This gene codes for the enzyme that functions as the rate limiting step in phosphatidylcholine biosynthesis in the Kennedy pathway which is critical for stored lipid metabolism and progeny development. Experimental removal ofWigglesworthiaimpaired lipid metabolism via disruption of the Kennedy pathway, yielding obese mothers whose developing progeny ultimately starve. Functional validation via experimentalcct1suppression revealed a phenotype similar to females lacking obligateWigglesworthiasymbionts. These results indicate that, inGlossina, symbiont-derived factors, likely B vitamins, are critical for proper function of both lipid biosynthesis and lipolysis. Loss of the symbiosis has a dramatic impact onGlossinafecundity, and may be broadly applicable to other insect systems, particularly to species that require symbiotic partners to maximize lipolysis and reproductive output.
DeDoc2 identifies and characterizes the hierarchy and dynamics of chromatin TAD-like domains in the single cells
Authors: Li Angsheng , Zeng Guangjie , Wang Haoyu , Li Xiao , Zhang Zhihua
Published: August 2022

Topologically associating domains (TAD) are functional chromatin units with hierarchical structure. However, the existence, prevalence and dynamics of such hierarchy in single cells remain unexplored. Here, we report a new generation TAD-like domain (TLD) detection algorithm, named deDoc2, to decode the hierarchy of TLDs in single cells. With dynamic programming, deDoc2 seeks genome partitions with global minimal structure entropy for both whole and local contact matrix. Compared to state-of-the-art tools, deDoc2 can uniquely identify the hierarchy of TLDs in single cells, in addition to outperforming its competitors. By applying deDoc2, we showed that the hierarchy of TLDs in single cells is highly dynamic during cell cycle, as well as among human brain cortex cells, and that it is associated with cellular identity and functions. Thus, our results demonstrated the abundance of information potentially encoded by TLD hierarchy for functional regulation. The deDoc2 can be freely accessed at https://github.com/zengguangjie/deDoc2.
Synthetic fibrous hydrogels as a platform to decipher cell-matrix mechanical interactions
Authors: Yuan Hongbo , Liu Kaizheng , Cóndor Mar , Barrasa-Fano Jorge , Louis Boris , Vandaele Johannes , de Almeida Paula , Coucke Quinten , Chen Wen , Oosterwijk Egbert , Xing Chenfen , Van Oosterwyck Hans , Kouwer Paul H. J. , Rocha Susana
Published: August 2022

The interactions between cells and their direct environment are crucial for cell fate but biochemically and mechanically highly complex, and therefore, poorly understood. Despite recent advances that exposed the impact of a range of different factors, real progress remains challenging, since appropriate controllable matrices and quantitative analysis techniques that cover a range of time and length scales are unavailable. Here, we use a synthetic fibrous hydrogel with nonlinear mechanics to mimic and tailor the bi-directional cell-matrix interactions. Using advanced microscopy-based approaches, we acquire a comprehensive picture of how cellular traction forces, fiber remodeling, matrix stiffening, matrix properties and cellular behavior interact, highlighting for instance, the importance of a fibrous architecture and nonlinear mechanics of the matrix. Complete mapping of cell-matrix interactions at the cellular length scale provides indispensable information for the rational design of biomimetic materials to recreate realistic in vitro cell environments.
Context-Aware Technology Mapping in Genetic Design Automation
Authors: Engelmann Nicolai , Schwarz Tobias , Kubaczka Erik , Hochberger Christian , Koeppl Heinz
Published: August 2022

Genetic design automation (GDA) tools hold promise to speed-up circuit design in synthetic biology. Their wide-spread adoption is hampered by their limited predictive power, resulting in frequent deviations between in-silico and in-vivo performance of a genetic circuit. Context-effects, i.e., the change in overall circuit functioning, due to the intracellular environment of the host and due to cross-talk among circuits components are believed to be a major source for the aforementioned deviations. Incorporating these effects in computational models of GDA tools is challenging but is expected to boost their predictive power, and hence, their deployment. Using fine-grained thermodynamic models of promoter activity we show in this work, how to account for two major components of cellular context effects: (i) Crosstalk due to limited specificity of used regulators and (ii) titration of circuit regulators to off-target binding sites on the host genome. We show, how we can compensate the incurred increase in computational complexity through dedicated branch-and-bound techniques during the technology mapping process. Using the synthesis of several combinational logic circuits based on Cello’s device library as a case study, we analyze the effect of different intensities and distributions of crosstalk on circuit performance and on the usability of a given device library.
Identifying climatic drivers of hybridization in Heuchereae (Saxifragaceae)
Authors: Folk R.A. , Gaynor M.L. , Engle-Wrye N.J. , O’Meara B.C. , Soltis P.S. , Soltis D.E. , Guralnick R.P. , Smith S.A. , Grady C.J. , Okuyama Y.
Published: August 2022

Applications of molecular phylogenetic approaches have uncovered evidence of hybridization across numerous clades of life, yet the environmental factors responsible for driving opportunities for hybridization remain obscure. Verbal models implicating geographic range shifts that brought species together during the Pleistocene have often been invoked, but quantitative tests using paleoclimatic data are needed to validate these models. Here, we produce a phylogeny for Heuchereae, a clade of 15 genera and 83 species in Saxifragaceae, with complete sampling of recognized species, using 277 nuclear loci and nearly complete chloroplast genomes. We then employ an improved framework with a coalescent simulation approach to test and ultimately confirm previous hybridization hypotheses and identify one new intergeneric hybridization event. Focusing on the North American distribution of Heuchereae, we introduce and implement a newly developed approach to reconstruct potential past distributions for ancestral lineages across all species in the clade and across a paleoclimatic record extending from the late Pliocene. Time calibration based on both nuclear and chloroplast trees recovers a mid- to late-Pleistocene date for most inferred hybridization events, a timeframe concomitant with repeated geographic range restriction into overlapping refugia. Our results indicate an important role for past episodes of climate change, and the contrasting responses of species with differing ecological strategies, in generating novel patterns of range contact among plant communities and therefore new opportunities for hybridization.
Cross-amplified Barcodes on Slides for Spatial Transcriptomics Sequencing
Authors: Jin Zhengyang , Yu Nianzuo , Bai Junda , Liu Zhiyi , Li Hongrui , Zhang Junhu , Liang Chongyang
Published: August 2022

Spatial transcriptomics can reveal molecular signatures of tissue at spatial scales, but current technologies cannot integrate excellent accessibility and easy data-decoding. Here, we use oligonucleotides whose number is the square root of the number of spots to generate cross-amplified spatial barcodes on slides using microfluidic technology. This method can obtain microarrays with well-defined barcodes easily and at low cost, without post-decoding, which contributes to the popularization of spatial transcriptomics.
La révolution de l’ADN: biocompatible and biosafe DNA data storage
Authors: Maes Alexandre , Le Peillet Jeanne , Julienne Achille , Blachon Clémence , Cornille Nicolas , Gibier Mariette , Arwani Erfane , Xu Zhou , Crozet Pierre , Lemaire Stéphane D.
Published: August 2022

DNA data storage is an emerging technology that has the potential to replace bulky, fragile and energy-intensive current digital data storage media. Here, we report a storage strategy called DNA Drive, that organizes data on long double stranded replicative DNA molecules. The DNA Drive has unlimited storage capacity, and its encoding scheme ensures the biosafety of the process by limiting the potential of the DNA sequence to code for mRNA and proteins. Using our approach, we encoded two historical texts from the French Revolution, the Declaration of the Rights of Man and of the Citizen of 1789 and the Declaration of the Rights of Woman and of the Female Citizen published in 1791. In contrast to previous DNA storage strategies, the biocompatibility of the DNA Drive enables biological manipulation of the data including low cost copy.

One-Sentence Summary

The DNA Drive is a biosafe and biocompatible DNA data storage strategy with unlimited storage capacity.
Full structure/function analysis of all the pilin subunits in a type 4 pilus: a complex of minor pilins in Streptococcus sanguinis mediates binding to glycans
Authors: Shahin Meriam , Sheppard Devon , Raynaud Claire , Berry Jamie-Lee , Gurung Ishwori , Silva Lisete M. , Feizi Ten , Liu Yan , Pelicic Vladimir
Published: August 2022

Type 4 filaments (T4F) – of which type 4 pili (T4P) are the archetype – are a superfamily of filamentous nanomachines nearly ubiquitous in prokaryotes. T4F are polymers of one major pilin that also contain minor pilins whose roles are often poorly understood. Here, we complete the structure/function analysis of the full set of T4P pilins in the opportunistic pathogen Streptococcus sanguinis. We determined the structure of the minor pilin PilA, which is unexpectedly similar to one of the subunits of a tip-located complex of four minor pilins, widely conserved in T4F. We found that PilA interacts and dramatically stabilises the minor pilin PilC. We determined the structure of PilC, showing that it is a modular pilin with a lectin module binding a specific subset of glycans prevalent in the human glycome, the host of S. sanguinis. Altogether, our findings support a model whereby the minor pilins in S. sanguinis T4P form a tip-located complex promoting adhesion to various host receptors. Our findings have general implications for a group of minor pilins widely conserved in T4F.
Characterization of a novel estrogen- and progesterone-responsive endometrial cancer cell line: HCI-EC-23
Authors: Rush Craig M. , Blanchard Zannel , Polaski Jacob T. , Osborne Kyle S. , Osby Krystle , Vahrenkamp Jeffery M. , Yang Chieh-Hsiang , Lum David H. , Hagan Christy R. , Leslie Kimberly K. , Pufall Miles A. , Thiel Kristina W. , Gertz Jason
Published: August 2022

Most endometrial cancers express the hormone receptor estrogen receptor alpha (ER) and are driven by excess estrogen signaling. However, evaluation of the estrogen response in endometrial cancer cells has been limited by the availability of hormonally responsivein vitromodels, with one cell line, Ishikawa, being used in most studies. Here, we describe a novel, adherent endometrioid endometrial cancer (EEC) cell line model, HCI-EC-23. We show that HCI-EC-23 retains ER expression and that ER functionally responds to estrogen induction over a range of passages. We also demonstrate that this cell line retains paradoxical activation of ER by tamoxifen, which is also observed in Ishikawa and is consistent with clinical data. The mutational landscape shows that HCI-EC-23 is mutated at many of the commonly altered genes in EEC, has relatively few copy-number alterations, and is microsatellite instable high (MSI-high).In vitroproliferation of HCI-EC-23 is strongly reduced upon combination estrogen and progesterone treatment. HCI-EC-23 exhibits strong estrogen dependence for tumor growthin vivoand tumor size is reduced by combination estrogen and progesterone treatment. Molecular characterization of estrogen induction in HCI-EC-23 revealed hundreds of estrogen-responsive genes that significantly overlapped with those regulated in Ishikawa. Analysis of ER genome binding identified similar patterns in HCI-EC-23 and Ishikawa, although ER exhibited more bound sites in Ishikawa. This study demonstrates that HCI-EC-23 is an estrogen- and progesterone-responsive cell line model that can be used to study the hormonal aspects of endometrial cancer.
SnFFPE-Seq: towards scalable single nucleus RNA-Seq of formalin-fixed paraffin-embedded (FFPE) tissue
Authors: Chung Hattie , Melnikov Alexandre , McCabe Cristin , Drokhlyansky Eugene , Van Wittenberghe Nicholas , Magee Emma M. , Waldman Julia , Spira Avrum , Chen Fei , Mazzilli Sarah , Rozenblatt-Rosen Orit , Regev Aviv
Published: August 2022

Profiling cellular heterogeneity in formalin-fixed paraffin-embedded (FFPE) tissues is key to characterizing clinical specimens for biomarkers, therapeutic targets, and drug responses. Here, we optimize methods for isolating intact nuclei and single nucleus RNA-Seq from FFPE tissues in the mouse brain, and demonstrate a pilot application to a human clinical specimen of lung adenocarcinoma. Our method opens the way to broad applications of snRNA-Seq to archival tissues, including clinical samples.
Gut Microbiome Signatures of Yorkshire Terrier Enteropathy during Disease and Remission
Authors: Doulidis Pavlos G. , Galler Alexandra I. , Hausmann Bela , Berry David , Rodríguez-Rojas Alexandro , Burgener Iwan A.
Published: August 2022

The role of the gut microbiome in developing Inflammatory Bowel Disease (IBD) in humans and dogs has received attention in recent years. Evidence suggests that IBD is associated with alterations in gut microbial composition, but further research is needed in veterinary medicine. The impact of IBD treatment on the gut microbiome needs to be better understood, especially in a breed-specific form of IBD in Yorkshire Terriers known as Yorkshire Terrier Enteropathy (YTE). This study aimed to investigate the difference in gut microbiome composition between YTE dogs during disease and remission and healthy Yorkshire Terriers. Our results showed a significant increase in specific taxa such asClostridium sensu stricto1,Escherichia-Shigella, andStreptococcus, and a decrease inBacteroides, Prevotella, Alloprevotella, andPhascolarctobacteriumin YTE dogs compared to healthy controls. No significant difference was found between the microbiome of dogs in remission and those with active disease, suggesting that the gut microbiome is affected beyond clinical recovery.
The rate of spontaneous mutations in yeast deficient for MutSβ function
Authors: Plavskin Yevgeniy , de Biase Maria Stella , Schwarz Roland F , Siegal Mark L.
Published: August 2022

Mutations in simple sequence repeat loci underlie many inherited disorders in humans, and are increasingly recognized as important determinants of natural phenotypic variation. In eukaryotes, mutations in these sequences are primarily repaired by the MutSβ mismatch repair complex. To better understand the role of this complex in mismatch repair and the determinants of simple sequence repeat mutation predisposition, we performed mutation accumulation in yeast strains with abrogated MutSβ function. We demonstrate that mutations in simple sequence repeat loci in the absence of mismatch repair are primarily deletions. We also show that mutations accumulate at drastically different rates in short (<8 bp) and longer repeat loci. These data lend support to a model in which the mismatch repair complex is responsible for repair primarily in longer simple sequence repeats.
Extreme sensitivity of fitness to environmental conditions; lessons from #1BigBatch
Authors: Kinsler  , Schmidlin  , Newell  , Eder  , Apodaca  , Lam  , Petrov  , Geiler-Samerotte
Published: August 2022

The phrase “survival of the fittest” has become an iconic descriptor of how natural selection works. And yet, precisely measuring fitness, even for single-celled microbial populations growing in controlled laboratory conditions, remains a challenge. While numerous methods exist to perform these measurements, including recently developed methods utilizing DNA barcoding, all methods seem limited in their precision to differentiate strains with small fitness differences. This limit on precision is relevant in many fields, including the field of experimental evolution. In this study, we hone in on the factors that contribute to noisy fitness measurements and suggest solutions to avoid certain sources of noise. Surprisingly, even when common sources of technical noise are controlled for, we find that fitness measurements are still very noisy. Our data suggest that subtle environmental differences among replicates create substantial variation across fitness measurements. We conclude by providing best practices for obtaining precise fitness measurements and by discussing how these measurements should be interpreted given their extreme context dependence. This work was inspired by the scientific community who followed us and gave us tips as we live-tweeted a high-replicate fitness measurement experiment at #1BigBatch.
Long-term NAD+ supplementation prevents the progression of age-related hearing loss in mice
Authors: Okur Mustafa N. , Kimura Risako , Sahbaz Burcin Duan , Manor Uri , Patel Jaimin , Andrade Leo , Puligilla Kala , Croteau Deborah L. , Bohr Vilhelm A.
Published: August 2022

Age-related hearing loss (ARHL) is the most common sensory disability associated with human aging. Yet, there are no approved measures for preventing or treating this debilitating condition. With its slow progression, continuous and safe approaches are critical for ARHL treatment. Nicotinamide Riboside (NR), a NAD+ precursor, is well tolerated even for long-term use and is already shown effective in various disease models including Alzheimer’s and Parkinson’s Disease. It has also been beneficial against noise induced hearing loss and in hearing loss associated with premature aging. However, its beneficial impact on ARHL is not known. Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL. Through transcriptomic and biochemical analysis, we find that NR administration restores age-associated reduction in cochlear NAD+ levels, upregulates biological pathways associated with synaptic transmission and PPAR signaling, and reduces the number of orphan ribbon synapses between afferent auditory neurons and inner hair cells. We also find that NR targets a novel pathway of lipid droplets in the cochlea by inducing the expression of CIDEC and PLIN1 proteins that are downstream of PPAR signaling and are key for lipid droplet growth. Taken together, our results demonstrate the therapeutic potential of NR treatment for ARHL and provide novel insights into its mechanism of action.
Disclosure of Gender Identity among Transgender Individuals to Healthcare Professionals in China: An Online Cross-sectional Study
Authors: Chauma Shamen Susan , Wan Chengsong , Dong Willa , Fu Xuezhen , Tucker Joseph D , Marley Gift , Tang Weiming
Published: August 2022

Purpose

Culture and stigma-relevant issues discourage transgender (TG) individuals in China from disclosing their gender identities. This limits their access to transgender competent health services. This study evaluates the factors associated with gender identity disclosure to health professionals among transgender individuals in China.

Methods

A cross-sectional study was conducted in nine cities across mainland China from December 2019 to June 2020 among transgender individuals. Participants completed questions covering socio-demographic information, HIV/STI testing, sexual behaviors, and access to medical and mental health services.

Results

Overall, 277 (85.5%) out of 324 transgender individuals were eligible to participate in the study. The mean age was 29±8 years old. Among them, 78% (192/277) had ever disclosed their gender identity to others, and 56% (155/277) had disclosed their gender identity to health professionals. 79.4% had ever tested for HIV (with an HIV prevalence of 9.1%), 47.3% had tested for other STIs, 42.6% had used hormone therapy, and 9.4% had undergone gender-affirming surgery. Results from the multivariable logistic regression demonstrated that compared to non-disclosers, disclosers were more likely to have tested for STIs (aOR=1.94, 95%CI: 1.12-3.39). Hormone intervention therapy (aOR=2.81, 95%CI: 1.56-5.05) and Pre-Exposure Prophylaxis (PrEP) use (aOR= 3.51, 95%CI: 1.12-10.97) were associated with gender identity disclosure to health professionals.

Conclusions

Low rates of gender identity disclosure to health professionals among transgender people may reflect fear of stigma and outing, suggesting the need for more trans-inclusive environments. More research is needed to understand the importance of disclosure in improving transgender health services.

A study among transgender individuals in nine cities across mainland China found that gender identity disclosers to health care professionals were more likely to test for STIs than nondisclosures.
Evolution of scapula size and shape in Carnivora: locomotor habits and differential shape scaling
Authors: Gálvez-López Eloy , Casinos Adrià
Published: August 2022

The effect of size, phylogeny, and locomotor habit, on shape was tested in 213 scapulas from 101 carnivoran species using 3D geometric morphometric methods. The sampled species spanned the whole size range and locomotor patterns in Carnivora. The results of the present study indicate that, in this order, scapula shape responds to the complex interaction of allometric, phylogenetic, and functional effects. Furthermore, evidence for differential scaling in the shape of the carnivoran scapula was found, which might be related to scaling differences among carnivoran families. Additionally, most allometric shape variation in the carnivoran scapula was related to size changes along phyletic lines. Locomotor-related shape differences were assessed using canonical variate analysis. Most locomotor habits could be significantly separated from each other based on scapula shape, although high misclassification rates were obtained when comparing semiarboreal and semifossorial carnivorans to other locomotor types. Locomotor indicators in the scapula shape of extant carnivorans seemed independent of size or shared ancestry and could be related to muscular function. These locomotor indicators were then used to infer the locomotor habits of several internal nodes of the carnivoran phylogeny, whose scapular size and shape was reconstructed using weighted square-change parsimony. According to scapula size and shape, the carnivoran ancestor was a medium-sized scansorial animal (i.e., it spent most of its time on the ground, but was a good climber).
Transcriptomics sheds light on N2-fixation strategies employed by a thermophilic member of theMethanococcales
Authors: Maslać Nevena , Sidhu Chandni , Teeling Hanno , Wagner Tristan
Published: August 2022

Some marine thermophilic methanogens are able to perform energy-consuming nitrogen fixation despite deriving only little energy from hydrogenotrophic methanogenesis. We studied this process inMethanothermococcus thermolithotrophicusDSM 2095, a methanogenic archaeon of the orderMethanococcales, that contributes to the nitrogen pool in some marine environments. We successfully grew this archaeon under diazotrophic conditions in both batch and fermenter cultures, reaching the highest cell density reported so far. Diazotrophic growth depended strictly on molybdenum and, in contrast to other diazotrophs, was not inhibited by tungstate or vanadate. This suggests an elaborate control of metal uptake and a specific metal recognition system for the insertion into the nitrogenase cofactor. Differential transcriptomics ofM. thermolithotrophicusgrown under diazotrophic conditions with ammonium-fed cultures as controls revealed upregulation of the nitrogenase machinery including chaperones, regulators, and molybdate-importers, as well as simultaneous upregulation of an ammonium-transporter and a putative pathway for nitrate/nitrite utilization. The organism thus employs multiple synergistic strategies for uptake of nitrogen nutrients during the early exponential growth phase without altering transcription levels for genes involved in methanogenesis. As a counterpart, genes coding for transcription and translation processes were downregulated, highlighting the maintenance of an intricate metabolic balance to deal with energy constraints and nutrient limitations imposed by diazotrophy. This switch in the metabolic balance included unexpected processes, such as upregulation of the CRISPR-Cas system, probably caused by drastic changes in transcription levels of putative mobile and virus-like elements.

Importance

The thermophilic anaerobic archaeon,M. thermolithotrophicus, is a particularly suitable model organism to study the coupling of methanogenesis to diazotrophy. Likewise, its capability to simultaneously reduce N2/CO2into NH3/CH4with H2makes it a viable target for biofuel production. We optimizedM. thermolithotrophicuscultivation, resulting in considerably higher cell yields and enabling the successful establishment of N2-fixing bioreactors. Improved understanding of the N2-fixation process would provide novel insights into metabolic adaptations that allow this energy-limited extremophile to thrive under diazotrophy, for instance by investigating its physiology and uncharacterized nitrogenase. We demonstrate that diazotrophic growth ofM. thermolithotrophicusis exclusively dependent on molybdenum, and complementary transcriptomics corroborated the expression of the molybdenum nitrogenase system. Further analyses of differentially expressed genes during diazotrophy across three cultivation time points revealed insights into the response to nitrogen limitation and the coordination of core metabolic processes.
A mixed-valence [CoII
4CoIII
2] cluster with defect disk-shaped topology
Authors: Yang Hua , Fu Yu-Pei , Huang Yuan , Chen Xiao-Li , Qiao Dan , Cui Hua-Li
Published: August 2022

The employment of the new Schiff base ligand 2-[(4-chloro-2-hydroxybenzylideneamino)methyl]phenol (H2
L) bearing O2N donors for the preparation of a novel Co6 cluster is reported. The hexanuclear cobalt complex, namely, di-μ2-acetatotetrakis{μ2-2-[(4-chloro-2-oxidobenzylideneamino)methyl]phenolato}tetra-μ3-methanolato-tetracobalt(II)dicobalt(III), [CoII
4CoIII
2(C14H10ClNO2)4(CH3COO)2(CH3O)4], was obtained using Co(CH3COO)2·4H2O and H2
L as starting materials in MeOH under solvothermal conditions. The six metal ions are linked together by the μ3-O atoms of four deprotonated MeOH molecules, two CH3COO− units and six phenolate O atoms of four L
2− ligands to form a defect disk-shaped topology. DC magnetic susceptibility investigations revealed the existence of antiferromagnetic interactions in the Co6 cluster.
A new two-dimensional cadmium(II) coordination polymer based on the asymmetric dicarboxylic acid homophthalic acid: synthesis, structure and properties
Authors: Shen Hong
Published: August 2022

A new coordination polymer poly[[μ2-4,4′-bis(2-methylimidazol-1-yl)biphenyl-κ2
N
3:N
3′]bis[μ3-2-(2-carboxylatophenyl)acetato-κ5
O,O′:O′,O′′:O′′]dicadmium(II)], [Cd(C9H6O4)(C20H18N4)0.5]
n
or [Cd(HMPH)(4,4′-BMIBP)0.5]
n
[H2HMPH is homophthalic acid and 4,4′-BMIBP is 4,4′-bis(2-methylimidazol-1-yl)biphenyl], (I), was synthesized by the solvothermal method and was structurally characterized by means of single-crystal X-ray diffraction, IR spectroscopy and elemental analysis. Coordination polymer (I) exhibits a two-dimensional layer based on one-dimensional [Cd(HMPH)]
n
chains. Remarkably, photocatalytic degradation experiments on methylene blue (MB) indicated that (I) exhibits an obvious degradation effect. Moreover, an investigation of the luminescence properties of (I) revealed that it could be considered as a potential highly selective luminescence sensor for nitrofurantoin (NFT).