bluuebunny/crossref_metadata_2025 huggingface dataset:
Ascending colon cecal junction carcinoma with prostate metastasis: A case report and literature review
Authors: Zhu Wanshan , Wu Jiaming , Wu Lexia , Meng Jincheng , Fang Cantu , Zhang Huatang
Published: March 2023

Rationale:

Colon carcinoma is the most common type of cancer, and a leading cause of cancer-related death. Clinically, the most common sites of metastases from colon carcinoma are the liver, lungs, peritoneum, and lymph nodes, while the incidence of metastases to the prostate is low. There are few relevant studies on colon carcinoma, most of them being case reports.

Patient concerns:

A 76-year-old man treated with radical resection of right colon carcinoma due to primary poorly differentiated adenocarcinoma of the cecum. Postoperative pathological examination suggested that he had cancer at the junction of the ascending colon and the cecum. He had received adjuvant chemotherapy after surgery. One year later, he received transurethral plasma resection of the prostate due to urinary system discomfort. Postoperative pathological immunohistochemistry suggested prostate metastasis of colorectal carcinoma, and he received individualized treatment, but this produced no clear survival benefit.

Diagnoses:

Ascending colon cecal junction carcinoma with prostate metastasis.

Interventions:

Radical resection, chemotherapy, anti-androgen therapy, surgery to relieve primary lesion obstruction symptoms, and local radiotherapy of the prostate.

Outcomes:

At present, clinical cases of colon carcinoma with prostate metastasis are rare. By sharing a rare case of ascending colon cecal junction carcinoma with prostate metastasis and reviewing the relevant literature, this paper explores and optimizes the clinical treatment of colon carcinoma with prostate metastasis.
A novel prognostic index based on the analysis of glycolysis-related genes in idiopathic pulmonary fibrosis
Authors: Li Yu , Deng Yaju , He Jie
Published: March 2023

Idiopathic pulmonary fibrosis (IPF) is a lung disease that is both chronic and progressive and is characterized by glycolysis. However, glycolysis’s function and its clinical significance in IPF are still not well understood.

We accessed the Gene Expression Omnibus database to retrieve mRNA expression information for lung tissue and other samples. We identified genes associated with glycolysis that had differential expression levels between IPF and controls. In this work, we conducted a comprehensive bioinformatic analysis to systematically examine the glycolysis-associated genes with differential expression and subsequently investigated the possible prognostic significance of these genes. Additionally, the expression profiles of the associated prognostic genes were further investigated via quantitative real-time polymerase chain reaction in our cohort. In this investigation, we found that the expression of 16 genes involved in glycolysis was differentially expressed. Among them, 12 were upregulated and 4 were downregulated. We found that 3 glycolysis-related genes (stanniocalcin 2, transketolase like 1, artemin) might serve as hub genes for anticipating patient prognosis. The data from these genes were used to generate the prognostic models. The findings confirmed that high-risk IPF patients recorded a shorter overall survival relative to low-risk patients. This prognostic model yielded 1-, 2-, and 3-year survival rates of 0.666, 0.651, and 0.717, correspondingly, based on the area under the curve of the survival-dependent receiver operating characteristic. The GSE27957 and GSE70866 cohorts validated these findings, indicating the model has a good predictive performance. All 3 glycolysis-associated genes were validated to be expressed in our cohort. Finally, we used mRNA levels from 3 genes to produce a nomogram to quantitatively predict the prognosis of IPF individuals. As possible indicators for the prognosis of IPF, the glycolysis-related genes stanniocalcin 2, transketolase like 1, and artemin were shown to be promising candidate markers.
The Safety of Performing Surgery at Ambulatory Surgery Centers Versus Hospital Outpatient Departments in Older Patients With or Without Multimorbidity
Authors: Silber Jeffrey H. , Rosenbaum Paul R. , Reiter Joseph G. , Jain Siddharth , Ramadan Omar I. , Hill Alexander S. , Hashemi Sean , Kelz Rachel R. , Fleisher Lee A.
Published: March 2023

Background:

Surgery for older Americans is increasingly being performed at ambulatory surgery centers (ASCs) rather than hospital outpatient departments (HOPDs), while rates of multimorbidity have increased.

Objective:

To determine whether there are differential outcomes in older patients undergoing surgical procedures at ASCs versus HOPDs.

Research Design:

Matched cohort study.

Subjects:

Of Medicare patients, 30,958 were treated in 2018 and 2019 at an ASC undergoing herniorrhaphy, cholecystectomy, or open breast procedures, matched to similar HOPD patients, and another 32,702 matched pairs undergoing higher-risk procedures.

Measures:

Seven and 30-day revisit and complication rates.

Results:

For the same procedures, HOPD patients displayed a higher baseline predicted risk of 30-day revisits than ASC patients (13.09% vs 8.47%,P< 0.0001), suggesting the presence of considerable selection on the part of surgeons. In matched Medicare patients with or without multimorbidity, we observed worse outcomes in HOPD patients: 30-day revisit rates were 8.1% in HOPD patients versus 6.2% in ASC patients (P< 0.0001), and complication rates were 41.3% versus 28.8%,P< 0.0001. Similar patterns were also found for 7-day outcomes and in higher-risk procedures examined in a secondary analysis. Similar patterns were also observed when analyzing patients with and without multimorbidity separately.

Conclusions:

The rates of revisits and complications for ASC patients were far lower than for closely matched HOPD patients. The observed initial baseline risk in HOPD patients was much higher than the baseline risk for the same procedures performed at the ASC, suggesting that surgeons are appropriately selecting their riskier patients to be treated at the HOPD rather than the ASC.
Intestinal Failure-Associated Liver Disease and Growth Pre- and Post-Transition to a Composite Lipid Emulsion
Authors: Hudson Alexandra S. , Tyminski Nicole , Turner Justine M. , Silverman Jason A.
Published: March 2023

Objectives:

Infants with intestinal failure have an increased risk of intestinal failure-associated liver disease (IFALD). Composite intravenous lipid emulsion (ILE) may reduce the risk of cholestasis. The primary outcome was to compare IFALD rates in infants with intestinal failure, between those receiving a composite ILE versus soybean oil ILE. The secondary outcome compared growth between these 2 groups.

Methods:

At our 2 tertiary neonatal/pediatric hospitals, we identified all patients (≤1 year old) who received ≥6 weeks parenteral nutrition (PN) from 2010 to 2018. Data included liver and growth parameters. IFALD was defined as serum conjugated bilirubin (CB) >33 µmol/L (≥2 mg/dL). Nonparametric tests were used for all comparisons.

Results:

Fifty infants (35 composite ILE, 15 soybean oil ILE) were included. Those on composite ILE received PN for longer (10.1 vs 7.6 weeks; P = 0.001) and had higher baseline CB (29 vs 6.5 μmol/L; P = 0.001). No differences were found by 6 weeks (14.5 vs 5 μmol/L; P = 0.54) and by PN cessation (4 vs 4 μmol/L; P = 0.33). The proportion of patients with IFALD decreased from 54% to 20% for composite ILE, while stable given soybean oil ILE (7%). There were no differences in weight, length, or head circumference z scores (P > 0.05).

Conclusions:

In our institutions, over 8 years, chronic intestinal failure was rare. Composite ILE was the predominant lipid choice for infants who needed longer courses of PN or had developed cholestasis. Despite longer PN duration, and higher baseline CB, overall rates of IFALD decreased with composite ILE. Regardless of parenteral lipid used, there were no differences in growth.
Natural History of Anemia and Efficacy and Safety of Oral Iron Therapy in Children Newly Diagnosed With Inflammatory Bowel Disease
Authors: D’Arcangelo Giulia , Distante Manuela , Veraldi Silvio , Tarani Francesca , Musto Francesca , Aloi Marina
Published: March 2023

Objectives:

Anemia is one of the most common extraintestinal manifestations of pediatric inflammatory bowel disease (IBD). We aimed to evaluate the prevalence of anemia in children newly diagnosed with IBD and assess the efficacy and safety of oral iron therapy over a 12-month follow-up period.

Methods:

This single-center, retrospective, observational cohort study included all children newly diagnosed with IBD at the Pediatric Gastroenterology Unit of Sapienza University of Rome from May 2015 to May 2019 presenting with anemia. At baseline, demographic, clinical, laboratory data (hemoglobin, mean corpuscular volume, serum iron, ferritin, transferrin levels, erythrocyte sedimentation rate, and C-reactive protein), and treatment received, were recorded. Clinical and laboratory data, as well as anemia therapy and adverse events (AEs), were collected every 3 months during the 1-year follow-up.

Results:

Eighty-nine out of 140 patients newly diagnosed with IBD presented with anemia (64%); 13 were excluded due to incomplete follow-up, thus 76 were included [median age 12.7 (interquartile range 9.8–15), 25 (33%) Crohn disease, 51 (67%) ulcerative colitis]. All patients received sucrosomial iron (SI) alone or in combination with intravenous ferric carboxymaltose. Treatment with SI was effective in 67 (88%) patients at the end of follow-up [37 (48%) within 3 months], regardless of anemia severity at baseline. No serious AEs related to SI treatment were reported.

Conclusions:

We confirmed a high prevalence of anemia at the time of the diagnosis of pediatric IBD. Our data suggest that SI is safe and effective, leading to anemia resolution in approximately half of the patients within 3 months.
Suicidal Behavior and Early Maladaptive Schemas and Schema Domains
Authors: Paula Milesi Idiana , Moreno Ferro de Araújo Rafael , Bücker Joana
Published: March 2023

Suicidal behavior is a risk factor for suicide attempts. Identifying the factors that increase suicidal behavior risk is paramount for overall suicide prevention efforts. One model that may contribute to our understanding of the relationship between early life experiences and suicidal behavior is the schema theory. This study aimed to examine suicidal behavior, early maladaptive schemas (EMSs), and schema domains using a large Brazilian nonclinical sample. The study included 19,060 individuals. We assessed sociodemographic variables, suicidal behavior (Suicidal Behavior Questionnaire), and EMSs (Young Schema Questionnaire) using an online, Web-based survey. Our results showed that, when comparing participants with no ideation with those with serious suicide attempts, we found significant statistical differences in all EMSs (all p's < 0.05), with higher scores in those with serious suicide attempts. Our results suggest that specific unmet emotional needs during childhood can affect mental health and result in serious suicide attempts in adulthood.
Challenges in the Head and Neck Department in the Diagnosis and Surgical Treatment of Patients Presenting to a Single Tertiary Hospital of Somalia With Extreme War Injuries
Authors: Yasar Mehmet , Ali Ismail Mohammed , Bayram Ali , Korkmaz Ufuk Turan Kursat , Sahin Murat , Irmak Saban
Published: March 2023

In this study, the authors aimed to share their experience with 46 patients who were wounded due to terrorism and war in Somalia. The authors also evaluated the etiological diversity of terror-related and war-related injuries. The study included 46 patients treated at the 150-bed Turkey-Somalia Tertiary Hospital between 2019 and 2021. The authors reviewed medical records including data regarding age, sex, trauma etiology, and type of fracture and trauma. For all patients, surgical technique and plate and screw applications were recorded. The authors also assessed complications and outcomes for the patients. The study included 5 women (10.9%) and 41 men (89.1%). The mean age was 30.36 years. It was found that 2 patients (4.35%) presented to the emergency department with stab injuries, 33 patients with blast injuries from improvised explosive devices (71.73%), and 11 patients with firearm injuries. There were 31 cases with maxillary and mandibular fractures, 17 of which had both maxillary and mandibular fractures. There were 14 patients with maxillary fracture alone, including 3 patients with tripod fracture and 7 patients with inferior and lateral rim fracture. There was a mandibular fracture in 17 patients, including 5 patients with parasymphysis fracture, 7 patients with ramus fracture, and 5 patients with multifocal comminuted fracture. It is a challenging process to treat terror-related injuries in our tertiary hospital in Somalia, where all resources are imported from foreign countries. In such settings, authorities should make protective equipment obligatory to prevent civil and military casualties. Trauma hospitals and experienced trauma surgeons should be available.
Survey of Pediatric ICU EEG Monitoring–Reassessment After a Decade
Authors: Fung France W. , Carpenter Jessica L. , Chapman Kevin E. , Gallentine William , Giza Christopher C. , Goldstein Joshua L. , Hahn Cecil D. , Loddenkemper Tobias , Matsumoto Joyce H. , Press Craig A. , Riviello James J. , Abend Nicholas S.
Published: March 2023

Purpose:

In 2011, the authors conducted a survey regarding continuous EEG (CEEG) utilization in critically ill children. In the interim decade, the literature has expanded, and guidelines and consensus statements have addressed CEEG utilization. Thus, the authors aimed to characterize current practice related to CEEG utilization in critically ill children.

Methods:

The authors conducted an online survey of pediatric neurologists from 50 US and 12 Canadian institutions in 2022.

Results:

The authors assessed responses from 48 of 62 (77%) surveyed institutions. Reported CEEG indications were consistent with consensus statement recommendations and included altered mental status after a seizure or status epilepticus, altered mental status of unknown etiology, or altered mental status with an acute primary neurological condition. Since the prior survey, there was a 3- to 4-fold increase in the number of patients undergoing CEEG per month and greater use of written pathways for ICU CEEG. However, variability in resources and workflow persisted, particularly regarding technologist availability, frequency of CEEG screening, communication approaches, and electrographic seizure management approaches.

Conclusions:

Among the surveyed institutions, which included primarily large academic centers, CEEG use in pediatric intensive care units has increased with some practice standardization, but variability in resources and workflow were persistent.
Flow regimes in a very wide-gap Taylor–Couette flow with counter-rotating cylinders
Authors: Merbold S. , Hamede M. H. , Froitzheim A. , Egbers C.
Published: March 2023

In this study, we discuss the observed flow regimes in Taylor–Couette flow of radius ratio

η
=
0.1

for various Reynolds numbers up to

1.5
×

10
4

. We investigate the flow using a visualization method. The flow states in the centrifugally unstable flow are investigated in the case of counter-rotating cylinders and pure inner cylinder rotation. Beside classical known flow states as Taylor-vortex flow and wavy vortex flow, we observe a variety of new flow structures in the cylindrical annulus, especially for the transition to turbulence. Coexisting turbulent and laminar regions inside the system are observed. Turbulent spots and turbulent bursts are observed, as well as an irregular Taylor-vortex flow and non-stationary turbulent vortices. Especially, a single axially aligned columnar vortex between the inner and outer cylinder is found. The principal regimes observed in flow between independently rotating cylinders are summarized in a flow-regime diagram.

This article is part of the theme issue ‘Taylor–Couette and related flows on the centennial of Taylor’s seminal
Philosophical Transactions
paper (part 2)’.
Routes to turbulence in Taylor–Couette flow
Authors: Feldmann Daniel , Borrero-Echeverry Daniel , Burin Michael J. , Avila Kerstin , Avila Marc
Published: March 2023

Fluid flows between rotating concentric cylinders exhibit two distinct routes to turbulence. In flows dominated by inner-cylinder rotation, a sequence of linear instabilities leads to temporally chaotic dynamics as the rotation speed is increased. The resulting flow patterns occupy the whole system and sequentially lose spatial symmetry and coherence in the transition process. In flows dominated by outer-cylinder rotation, the transition is abrupt and leads directly to turbulent flow regions that compete with laminar ones. We here review the main features of these two routes to turbulence. Bifurcation theory rationalizes the origin of temporal chaos in both cases. However, the catastrophic transition of flows dominated by outer-cylinder rotation can only be understood by accounting for the spatial proliferation of turbulent regions with a statistical approach. We stress the role of the rotation number (the ratio of Coriolis to inertial forces) and show that it determines the lower border for the existence of intermittent laminar–turbulent patterns.

This article is part of the theme issue ‘Taylor–Couette and related flows on the centennial of Taylor’s seminalPhilosophical Transactionspaper (part 2)’.
Thermo-fluid dynamics and synergistic enhancement of heat transfer by interaction between Taylor–Couette flow and heat convection
Authors: Masuda Hayato , Nakagawa Kanta , Iyota Hiroyuki , Wang Steven , Ohmura Naoto
Published: March 2023

This study experimentally and numerically investigated the thermo-fluid dynamics of Taylor–Couette flow with an axial temperature gradient from the chemical engineering perspective. A Taylor–Couette apparatus with a jacket vertically divided into two parts was used in the experiments. Based on the flow visualization and temperature measurement for glycerol aqueous solutions with various concentrations, the flow pattern was classified into six modes: heat convection dominant mode (Case I), heat convection-Taylor vortex flow alternate mode (Case II), Taylor vortex flow dominant mode (Case III), fluctuation maintaining Taylor cell structure mode (Case IV), segregation between Couette flow and Taylor vortex flow mode (Case V) and upward motion mode (Case VI). These flow modes weremapped in terms of the Reynolds and Grashof numbers. Cases II, IV, V and VI are regarded as transition flow patterns between Case I and Case III, depending on the concentration. In addition, numerical simulations showed that in Case II, heat transfer was enhanced when the Taylor–Couette flow was altered by heat convection. Moreover, the average Nusselt number with the alternate flow was higher than that with the stable Taylor vortex flow. Thus, the interaction between heat convection and Taylor–Couette flow is an effective tool to enhance heat transfer.

This article is part of the theme issue ‘Taylor–Couette and related flows on the centennial of Taylor’s seminal
Philosophical transactions
paper (Part 2)’.
Dispersion and mixing dynamics of complex oil-in-water emulsions in Taylor–Couette flows
Authors: Panwar Vishal , Vargas Cassandra N. , Dutcher Cari S.
Published: March 2023

The seminal study by G. I. Taylor (1923) has inspired generations of work in exploring and characterizing Taylor–Couette (TC) flow instabilities and laid the foundation for research of complex fluid systems requiring a controlled hydrodynamic environment. Here, TC flow with radial fluid injection is used to study the mixing dynamics of complex oil-in-water emulsions. Concentrated emulsion simulating oily bilgewater is radially injected into the annulus between rotating inner and outer cylinders, and the emulsion is allowed to disperse through the flow field. The resultant mixing dynamics are investigated, and effective intermixing coefficients are calculated through measured changes in the intensity of light reflected by the emulsion droplets in fresh and salty water. The impacts of the flow field and mixing conditions on the emulsion stability are tracked via changes in droplet size distribution (DSD), and the use of emulsified droplets as tracer particles is discussed in terms of changes in the dispersive Péclet, Capillary and Weber numbers. For oily wastewater systems, the formation of larger droplets is known to yield better separation during a water treatment process, and the final DSD observed here is found to be tunable based on salt concentration, observation time and mixing flow state in the TC cell.

This article is part of the theme issue ‘Taylor–Couette and related flows on the centennial of Taylor’s seminal
Philosophical Transactions
paper (part 2)’.
Taylor–Couette flow in the narrow-gap limit
Authors: Nagata Masato
Published: March 2023

A Cartesian representation of the Taylor–Couette system in the vanishing limit of the gap between coaxial cylinders is presented, where the ratio,

μ

, of the angular velocities,

ω
i

and

ω
o

, of the inner and the outer cylinders, respectively, affects its axisymmetric flow structures. Our numerical stability study finds remarkable agreement with previous studies for the critical Taylor number,

T
c

(
μ
)

, for the onset of axisymmetric instability. The Taylor number

T

can be expressed as

T
=
Ω
(

R

−
Ω
)

, where

Ω

(the rotation number) and

R

(the Reynolds number) in the Cartesian system are related to the average and the difference of

ω
i

and

ω
o

. The instability sets in the region

(
Ω
,

R

)
→
(
0
,
∞
)

, while the product of

Ω

and

R

is kept finite. Furthermore, we developed a numerical code to calculate nonlinear axisymmetric flows. It is found that the mean flow distortion of the axisymmetric flow is antisymmetric across the gap when

μ
=
1

, while a symmetric part of the mean flow distortion appears additionally when

μ
≠
1

. Our analysis also shows that for a finite

R

all flows with

μ
≠
 
1

approach the

R

axis, so that the plane Couette flow system is recovered in the vanishing gap limit.

This article is part of the theme issue ‘Taylor–Couette and related flows on the centennial of Taylor’s seminal
Philosophical Transactions
paper (part 2)’.
Near-wall vortical structures in domains with and without curved surfaces
Authors: Sharma Manjul , Nair K. Aswathy , Vishnu R. , Sameen A.
Published: March 2023

Taylor–Couette flow is a canonical flow to study Taylor–Görtler (TG) instability or centrifugal instability and the associated vortices. TG instability has been traditionally associated with flow over curved surfaces or geometries. In the computational study, we confirm the presence of TG-like near-wall vortical structures in two lid-driven flow systems, the Vogel–Escudier (VE) and the lid-driven cavity (LDC) flows. The VE flow is generated inside a circular cylinder by a rotating lid (top lid in the present study), while the LDC flow is generated inside a square or rectangular cavity by the linear movement of the lid. We look at the emergence of these vortical structures through reconstructed phase space diagrams and find that the TG-like vortices are seen in the chaotic regimes in both flows. In the VE flow, these vortices are seen when the side-wall boundary layer instability sets in at large

R
e

. The VE flow is observed to go to a chaotic state in a sequence of events from a steady state at low

R
e

. In contrast to VE flows, in the LDC flow with no curved boundaries, TG-like vortices are seen at the emergence of unsteadiness when the flow exhibits a limit cycle. The LDC flow is observed to have transitioned to chaos from the steady state through a periodic oscillatory state. Various aspect ratio cavities are examined in both flows for the presence of TG-like vortices.

This article is part of the theme issue ‘Taylor–Couette and related flows on the centennial of Taylor’s seminal
Philosophical transactions
paper (Part 2)’.
Genomic discovery and functional validation of MRP1 as a novel fetal hemoglobin modulator and potential therapeutic target in sickle cell disease
Authors: Hara Yannis , Kawabata Emily , Lemgart Viktor T. , Bronson Paola G. , Hicks Alexandra , Peters Robert , Krishnamoorthy Sriram , Ribeil Jean-Antoine , Schmunk Lisa J. , Eglinton Jennifer , Watkins Nicholas A. , Roberts David J. , Di Angelantonio Emanuele , Danesh John , Astle William J. , Paul Dirk S. , Lessard Samuel , Butterworth Adam S.
Published: March 2023

Sickle cell disease (SCD) remains a major health burden with limited treatment options. Despite promising gene-editing clinical trials, there is an unmet need for cost-effective therapies. As induction of fetal hemoglobin (HbF) is an established therapeutic strategy for SCD, we conducted a genome-wide association study of circulating HbF levels in ~11,000 participants to identify further HbF modulators. We identified associations in 11 genomic regions, including eight novel loci such asABCC1(encoding multidrug resistance-associated protein 1, MRP1). Using gene-editing and pharmacological approaches, we showed that inhibition of MRP1 increases HbF, intracellular glutathione levels, and reduces sickling in erythroid cells from SCD patients. Overall, our findings identify several novel genetically-validated potential therapeutic targets for SCD, including promising proof-of-principle results from small molecule inhibition of MRP1.
Development and validation of a multivariate model for predicting heart failure hospitalization and mortality in patients receiving maintenance hemodialysis
Authors: Tang Wenwu , Yuan Xinzhu , Wang Zhixin , Zhang Ying , Chen Xiaoxia , Yang Xiaohua , Qi Zhirui , Zhang Ju , Li Jie , Xie Xisheng
Published: March 2023

Background

Heart failure (HF) is a common cardiovascular disease in patients receiving maintenance hemodialysis (MHD). Once these patients on MHD exhibit HF, their hospitalization rate, mortality, and economic burden will be significantly increased. Early identification and prediction of hospitalization and death are of great importance for reducing hospitalization and mortality. This study used multicenter clinical data to develop and externally validate clinical risk models to predict expected mortality and HF hospitalization rates in MHD patients with HF.

Materials and Methods

From January 2017 to October 2022, 348 patients receiving MHD from four participating centers were enrolled. Demographic data, MHD treatment modalities, laboratory tests, and echocardiography data were collected when the initial event occurred. Three centers were randomly assigned to the modeling dataset (n=258), and one center was assigned to the external validation set (n=90). Considering a composite outcome of HF hospitalization and death as the primary endpoint and hospitalization due to HF or death as the secondary endpoint, a COX clinical prediction model was constructed and verified using internal and external datasets.

Results

The median age of patients in the modeling cohort was 63 years old, 41.5% of patients were women; 165 (61%) had a history of HF; 81 (31.4%) were hospitalized for HF; and 39 (15.1%) patients had died. The c-statistic values for composite outcome, hospitalization for HF, and mortality were 0.812, 0.808, and 0.811, respectively. The predictors of death and hospitalization outcomes caused by HF are significantly different. The strongest predictors of HF hospitalization outcomes were advanced age, multiple HF hospitalizations, hyponatremia, high levels of NT-proBNP and hs-cTnT, and larger MVe values. The strongest predictors of mortality were longer dialysis age, combined atrial fibrillation, calcification of the aortic or mitral valve (especially calcification, and in particular aortic valve calcification), pleural effusion, low serum sodium, and higher levels of hs-cTnT. The median age of the patients in the external validation cohort was 63 years old; 28.8% were female; 35 (38.1%) had a history of HF; 11 (12.2%) were hospitalized for HF; and 5 (5.6%) died. The c-statistic of the predictive models for composite outcome, hospitalisation for HF, and mortality was comparable to that of the modelling cohort.

Conclusion

The model established in this study is stable and reliable and the included variables are easily obtained from the routine clinical environment. The model can provide useful risk factors and prognostic information for patients with MHD combined with HF. Keywords: heart failure, MHD patients, mortality, predictive model, external validation.
Hox genes modulate physical forces to differentially shape small and large intestinal epithelia
Authors: Gill Hasreet K. , Yin Sifan , Nerurkar Nandan L. , Lawlor John C. , Huycke Tyler R. , Mahadevan L. , Tabin Clifford J.
Published: March 2023

The small and large intestines arise from a common primordial gut tube but ultimately become specialized in both form and function. While the midgut forms villi, the hindgut develops flat, brain-like sulci that resolve into heterogeneous outgrowths. Gut compartment identities are demarcated early in development via Hox genes, which are highly conserved, master regulators of spatial patterning in the embryo. Yet, how these factors trigger regional morphogenesis has remained a mystery. Combining mechanical measurements and mathematical modeling, we demonstrate that the posterior Hox geneHoxd13regulates biophysical phenomena that shape the hindgut lumen. We further show thatHoxd13acts through the TGFβ pathway to thicken, stiffen, and promote isotropic growth of the subepithelial mesenchyme; together, these features generate hindgut surface patterns. TGFβ, in turn, promotes collagen deposition to affect mesenchymal geometry and growth. We thus identify a cascade of events downstream of genetic identity that direct posterior intestinal morphogenesis.
CRAPS: Chromosomal-Repair-Assisted Pathway Shuffling in yeast
Authors: Dykstra Christien B. , Pyne Michael E. , Martin Vincent J.J.
Published: March 2023

A fundamental challenge of metabolic engineering involves assembling and screening vast combinations of orthologous enzymes across a multi-step biochemical pathway. Current pathway assembly workflows involve combining genetic partsex vivoand assembling one pathway configuration per tube or well. Here we present CRAPS,Chromosomal-Repair-AssistedPathwayShuffling, anin vivopathway engineering technique that enables the self-assembly of one pathway configuration per cell. CRAPS leverages the yeast chromosomal repair pathway and utilizes a pool of inactive, chromosomally integrated orthologous gene variants corresponding to a target multi-step pathway. Supplying gRNAs to the CRAPS host activates the expression of one gene variant per pathway step, resulting in a unique pathway configuration in each cell. We deployed CRAPS to build more than 1,000 combinations of a four-step carotenoid biosynthesis network. Sampling the CRAPS pathway space yielded strains with distinct color phenotypes and carotenoid product profiles. We anticipate that CRAPS will expedite strain engineering campaigns by enabling the generation and sampling of vast biochemical spaces.
Comparative mitogenomics of native European and alien Ponto-Caspian amphipods
Authors: Macher Jan-Niklas , Šidagytė-Copilas Eglė , Copilaş-Ciocianu Denis
Published: March 2023

European inland surface waters harbor an extensive diversity of native amphipod crustaceans with many species facing threats from invasive counterparts of Ponto-Caspian origin. Herein, we examine mitochondrial genomes to infer phylogenetic relationships and compare gene order and nucleotide composition between representative native European and invasive Ponto-Caspian taxa belonging to five families, ten genera, and 20 species (13 newly sequenced herein). We observe diverse gene rearrangement patterns in the phylogenetically disparate native species pool.Pallaseopsis quadrispinosaandSynurella ambulansshow significant departures from the typical organization, with extensive translocations of tRNAs and the nad1 gene, as well as a tRNA-F polarity switch in the latter. The monophyletic alien Ponto-Caspian gammarids display a conserved gene order, mainly differing from the native species by a tRNA-E and tRNA-R translocation, which strengthens previous findings. However, extensive rearrangement is observed inChaetogammarus warpachowskyiwith translocations of six tRNAs. The alien corophiid,Chelicorophium curvispinum, displays a very conserved gene order despite its distant phylogenetic position. We also find that native species have a significantly higher GC and lower AT content than invasive ones. The observed mitogenomic differences between native and invasive amphipods need further investigation and could shed light on the mechanisms underlying invasion success.
Cysteine: an ancestral Cu binding ligand in green algae?
Authors: Strenkert Daniela , Schmollinger Stefan , Hu Yuntao , Hofmann Christian , Holbrook Kristen , Liu Helen W. , Purvine Samuel O. , Nicora Carrie D. , Chen Si , Lipton Mary S. , Northen Trent R. , Clemens Stephan , Merchant Sabeeha S.
Published: March 2023

Growth ofChlamydomonas reinhardtiiin zinc (Zn) limited medium leads to disruption of copper (Cu) homeostasis, resulting in up to 40-fold Cu over-accumulation relative to its typical Cu quota. We show that Chlamydomonas controls its Cu quota by balancing Cu import and export, which is disrupted in a Zn deficient cell, thus establishing a mechanistic connection between Cu and Zn homeostasis. Transcriptomics, proteomics and elemental profiling revealed that Zn-limited Chlamydomonas cells up-regulate a subset of genes encoding “first responder” proteins involved in sulfur (S) assimilation and consequently accumulate more intracellular S, which is incorporated into L-cysteine, γ-glutamylcysteine and homocysteine. Most prominently, in the absence of Zn, free L-cysteine is increased ~80-fold, corresponding to ~ 2.8 × 109molecules/cell. Interestingly, classic S-containing metal binding ligands like glutathione and phytochelatins do not increase. X-ray fluorescence microscopy showed foci of S accumulation in Zn-limited cells that co-localize with Cu, phosphorus and calcium, consistent with Cu-thiol complexes in the acidocalcisome, the site of Cu(I) accumulation. Notably, cells that have been previously starved for Cu do not accumulate S or Cys, causally connecting cysteine synthesis with Cu accumulation. We suggest that cysteine is anin vivoCu(I) ligand, perhaps ancestral, that buffers cytosolic Cu.
«In vitroandin vivocombination of lytic phages and octapeptin OPX10053 against β-lactamase-producing clinical isolates ofKlebsiella pneumoniae»
Authors: Pacios Olga , Blasco Lucia , Bleriot Ines , Fernández-García Laura , López María , Ortiz-Cartagena Concha , Barrio-Pujante Antonio , Fernández Cuenca Felipe , Aracil Belen , Oteo-Iglesias Jesús , Hansford Karl A. , Tomás María
Published: March 2023

Background

novel approaches to treatKlebsiella pneumoniaeinfections are desperately needed, such as the use of rationally designed combination therapies.

Objectives

to evaluate thein vitroandin vivotherapeutic potential of lytic phages againstK. pneumoniaein combination with octapeptin, a promising class of lipopeptides with broad spectrum Gram-negative activity.

Methods

we determined the MICs to twenty-two lipopeptide compounds and chose one octapeptin (OPX10053) for evaluation of potential synergism in combination with lytic phages using checkerboard assays, optical density growth curves and time-kill (CFU enumeration). Toxicity and efficacyin vivoassays were conducted onGalleria mellonellalarvae.

Results

this study reports the synergy foundin vitrobetween the octapeptin OPX10053 and two lytic phages previously characterized by our research group (vB_KpnM-VAC13 and vB_KpnM-VAC66) against clinical isolates ofK. pneumoniae. This synergy was validated by the FIC index, OD growth curves and time-kill assay when OPX10053 was added following 4 hours of phage exposure. Preliminary evaluation of toxicity revealed that OPX10053, even at subinhibitory concentrations and in phage combinations, exerts a toxic effect on larvae, which requires further investigation.

Conclusions

Thein vitroapplication of lytic phages in combination with octapeptin OPX10053 showed synergistic activity. Exposure ofG. mellonellato the lytic phages was well tolerated, whereas combination treatment with subinhibitory concentrations of OPX10053 did not attenuate toxicity. Even so, this innovative approach of combining lytic phages could open the door to some interesting associations between chemically synthesized drugs and biological entities. Sequential or simultaneous application alongside time, dosing and stewardship warrants further research.
Shared gene targets of the ATF4 and p53 transcriptional networks
Authors: Baniulyte Gabriele , Durham Serene A. , Merchant Lauren E. , Sammons Morgan A.
Published: March 2023

The master tumor suppressor p53 regulates multiple cell fate decisions, like cell cycle arrest and apoptosis, via transcriptional control of a broad gene network. Dysfunction in the p53 network is common in cancer, often through mutations that inactivate p53 or other members of the pathway. Induction of tumor-specific cell death by restoration of p53 activity without off-target effects has gained significant interest in the field. In this study, we explore the gene regulatory mechanisms underlying a putative anti-cancer strategy involving stimulation of the p53-independent Integrated Stress Response (ISR). Our data demonstrate the p53 and ISR pathways converge to independently regulate common metabolic and pro-apoptotic genes. We investigated the architecture of multiple gene regulatory elements bound by p53 and the ISR effector ATF4 controlling this shared regulation. We identified additional key transcription factors that control basal and stress-induced regulation of these shared p53 and ATF4 target genes. Thus, our results provide significant new molecular and genetic insight into gene regulatory networks and transcription factors that are the target of numerous antitumor therapies.
Cracking the floral quartet code: How do multimers of MIKCC-type MADS-domain transcription factors recognize their target genes?
Authors: Käppel Sandra , Rümpler Florian , Theißen Günter
Published: March 2023

MADS-domain transcription factors (MTFs) are involved in the control of many important processes in eukaryotes. They are defined by the presence of a unique and highly conserved DNA-binding domain, the MADS-domain. MTFs bind to double-stranded DNA as dimers and recognize specific sequences termed CArG-boxes (such as 5’-CC(A/T)6GG-3’) and similar sequences that occur hundreds of thousand times in a typical flowering plant genome. The number of MTF-encoding genes increased by about two orders of magnitude during land plant evolution, resulting in roughly about 100 genes in flowering plant genomes. This raises the question as to how dozens of different, but highly similar MTFs accurately recognize thecis-regulatory elements of diverse target genes when the core binding sequence (CArG-box) occurs at such a high frequency. Besides the usual processes, such as base and shape readout of individual DNA sequences by dimers of MTFs, an important sublineage of MTFs in plants, termed MIKCC-type MTFs (MC-MTFs) has evolved an additional mechanism to increase the accurate recognition of target genes: the formation of heterotetramers of closely related proteins that bind to two CArG-boxes on the same DNA strand involving DNA-looping. MC-MTFs control important developmental processes in flowering plants, ranging from root and shoot to flower, fruit and seed development. The way MC-MTFs bind to DNA and select their target genes is hence not only of high biological interest, but also of great agronomic and economic importance. In this article we review the interplay of the different mechanisms of target gene recognition, from the ordinary (base readout) via the extravagant (shape readout) to the idiosyncratic (recognition of the distance and orientation of two CArG-boxes by heterotetramers of MC-MTFs). A special focus of our treatment is on the structural prerequisites of MC-MTFs that enable the specific recognition of target genes.
Distribution ofblaCTX-M-gene variants inE. colifrom different origins in Ecuador
Authors: Valenzuela Xavier , Hedman Hayden , Villagomez Alma , Cardenas Paul , Eisenberg Joseph N. S. , Levy Karen , Zhang Lixin , Trueba Gabriel
Published: March 2023

The increasing abundance of extended spectrum β-lactamase (ESBL) genes inE. coli, and other commensal and pathogenic bacteria, endangers the utility of third or more recent generation cephalosporins, which are major tools for fighting deadly infections. The role of domestic animals in the transmission of ESBL carrying bacteria has been recognized, especially in low- and middle-income countries, however the horizontal gene transfer of these genes is difficult to assess. Here we investigateblaCTX-Mgene diversity (and flanking nucleotide sequences) inE. colifrom chicken and humans, in an Ecuadorian rural community and from chickens in another location in Ecuador. TheblaCTX-Massociated sequences in isolates from humans and chickens in the same remote community showed greater similarity from those found inE. coliin a chicken industrial operation 200 km away. Our study may provide evidence ofblaCTX-Mtransfer between chickens and humans in the community.
Deactivation and Collective Phasic Muscular Tuning for Pointing Direction: Insights from Machine Learning
Authors: Chambellant Florian , Gaveau Jeremie , Papaxanthis Charalambos , Thomas Elizabeth
Published: March 2023

Arm movements in our daily lives have to be adjusted for several factors in response to the demands of the environment, for example, speed, direction or distance. Previously, we had shown that arm movement kinematics is optimally tuned to take advantage of gravity effects and minimize muscle effort in various pointing directions and gravity contexts (Gaveau et al., 2016). Here we build upon these results and focus on muscular adjustments. We used Machine Learning to analyze the ensemble activities of multiple muscles recorded during pointing in various directions. The advantage of such a technique would be the observation of patterns in collective muscular activity that may not be noticed using univariate statistics. By providing an index of multimuscle activity, the Machine Learning analysis brought to light several features of tuning for pointing direction. In attempting to trace tuning curves, all comparisons were done with respects to pointing in the horizontal, gravity free plane. We demonstrated that tuning for direction does not take place in a uniform fashion but in a modular manner in which some muscle groups play a primary role. The antigravity muscles were more finely tuned to pointing direction than the gravity muscles. Of note, was their tuning during the first half of downward pointing. As the antigravity muscles were deactivated during this phase, it supported the idea that deactivation is not an on-off function but is tuned to pointing direction. Further support for the tuning of the portions of the phasic EMG containing only negative activity was provided by progressively improving classification accuracies with increasing angular distance from the horizontal. Overall, these results show that the motor system tunes muscle commands to exploit gravity effects and reduce muscular effort. It quantitatively demonstrates that phasic EMG negativity is an essential feature of muscle control.
Hyperspectral Oblique Plane Microscopy Enables Spontaneous, Label-Free Imaging of Biological Dynamic Processes in Live Animals
Authors: Guo Ke , Kalyviotis Konstantinos , Pantazis Periklis , Rowlands Christopher J
Published: March 2023

Spontaneous Raman imaging has emerged as powerful label-free technique for investigating the molecular composition of biological specimens. Although Raman imaging can facilitate understanding of complex biological phenomenain vivo, current imaging modalities are limited in speed and sample compatibility. Here, we introduce a single-objective light-sheet microscope, namedλ-OPM, which records Raman images on a timescale of minutes to milliseconds. To demonstrate its function, we useλ-OPM to map and identify micro-plastic particles based on their Raman spectral characteristics. In live zebrafish embryos, we show thatλ-OPM can capture wound dynamics at five-minute intervals, revealing rapid changes in cellular and extracellular matrix composition in the wounded region. Finally, we useλ-OPM to obtain Raman scattering maps of a zebrafish embryo’s beating heart at an effective 28 frames per second, recording compositional changes at different points in the cardiac cycle.
Spiny but photogenic: amateur sightings complement herbarium specimens to reveal the bioregions of cacti
Authors: Calvente Alice , da Silva Ana Paula Alves , Edler Daniel , Carvalho Fernanda Antunes , Fantinati Mariana Ramos , Zizka Alexander , Antonelli Alexandre
Published: March 2023

Premise

Cacti are characteristic elements of the Neotropical flora and of major interest for biogeographic, evolutionary, and ecological studies. Here we test global biogeographic boundaries for Neotropical Cactaceae using specimen-based occurrences coupled with data from visual observations, including citizen science records, as a means to tackle the known collection biases in the family.

Methods

Species richness and record density were assessed separately for preserved specimens and human observations and a bioregional scheme tailored to Cactaceae was produced using the interactive web application Infomap Bioregions based on data from 261,272 point records cleaned through automated and manual steps.

Key Results

We find that areas in Mexico and southwestern USA, Eastern Brazil and along the Andean region have the greatest density of records and the highest species richness. Human observations complement information from preserved specimens substantially, especially along the Andes. We propose 24 cacti bioregions, among which the most species-rich are, in decreasing order: northern Mexico/southwestern USA, central Mexico, southern central Mexico, Central America, Mexican Pacific coast, central and southern Andes, northwestern Mexico/extreme southwestern USA, southwestern Bolivia, northeastern Brazil, Mexico/Baja California.

Conclusions

The bioregionalization proposed shows novel or modified biogeographical boundaries specific to cacti, and can thereby aid further evolutionary, biogeographic, and ecological studies by providing a validated framework for further analyses. This classification builds upon, and is distinctive from, other expert-derived regionalization schemes for other taxa. Our results showcase how observation data, including citizen-science records, can complement traditional specimen-based data for biogeographic research, particularly for taxa with specific specimen collection and preservation challenges and those that are threatened or internationally protected.
Single-molecule acceptor rise time (smART) FRET for nanoscale distance sensitivity
Authors: Guo Jiajia , Chen Xuyan , Manna Premashis , Lin Xingcheng , Scott Madelyn N. , Chen Wei Jia , Hoffman Mikaila , Zhang Bin , Schlau-Cohen Gabriela S.
Published: March 2023

The structure, dynamics, and binding of individual biomolecules have been extensively investigated using single-molecule Förster resonance energy transfer (smFRET) as a ‘spectroscopic ruler.’ The FRET efficiency between a fluorophore pair is used to measure distances in the several nanometer range. Existing approaches to detect closer distances come at the expense of sensitivity to longer distances. Here, we introduce single-molecule acceptor rise-time (smART) FRET that spans closer and longer distances. The acceptor rise time encodes the FRET rate, which scales polynomially with distance and thus has a steep dependence that expands the working range by 50%. High precision and accuracy is achieved through the spectroscopic separation between the rise time and the photophysical fluctuations that obfuscate other FRET readouts. Using the nanoscale sensitivity, we resolved the architectures of DNA bound to the single-stranded binding protein fromE. coli, demonstrating the ability of smART FRET to elucidate the complex behaviors of biomolecules.