bluuebunny/crossref_metadata_2025 huggingface dataset:
A characterization of Whitney forms
Authors: Dodziuk Józef
Published: January 2024

We give a characterization of Whitney forms on an

n
n

-simplex

σ
\sigma

and prove that for every real valued simplicial

k
k

-cochain

c
c

on

σ
\sigma

, the form

W
c

Wc

is the unique differential

k
k

-form

φ
\varphi

on

σ
\sigma

with affine coefficients that pulls back to a constant form of degree

k
k

on every

k
k

-face

τ
\tau

of

σ
\sigma

, and satisfies

∫

τ

φ
=>
c
,
τ
>

\int _{\tau } \varphi = >c,\tau >

.
L-packets over strong real forms
Authors: Arancibia Robert N. , Mezo P.
Published: January 2024

Langlands [On the classification of irreducible representations of real algebraic groups, Math. Surveys Monogr., vol. 31, Amer. Math. Soc., Providence, RI, 1989, pp. 101–170] defined

L
L

-packets for real reductive groups. In order to refine the local Langlands correspondence, Adams-Barbasch-Vogan [The Langlands classification and irreducible characters for real reductive groups, Progress in Mathematics, vol. 104, Birkhäuser Boston, Inc., Boston, MA, 1992] combined L-packets over all real forms belonging to an inner class. In the tempered setting, using different methods, Kaletha [Ann. of Math. (2) 184 (2016), pp. 559–632] also defines such combined L-packets with a refinement to the local Langlands correspondence. We prove that the tempered L-packets of Adams-Barbasch-Vogan and Kaletha are the same and are parameterized identically.
Small money, large profits: how the cashless revolution aggravates social inequality
Authors: Brandl Barbara , Hengsbach David , Moreno Guadalupe
Published: January 2024

The replacement of cash by cashless alternatives carries huge potential to aggravate social inequality. Governments struggle to manage these dynamics since they must keep a delicate balance between the formation of strong players and the provision of inclusive payment options. Studying the political economy behind the payment industry is crucial to understanding how digitalization has transformed payments. To this aim, we look at the history of the payment industry in two cases: the USA and the euro area. In the USA, the cashless revolution gave rise to an oligopoly of two extremely successful credit card companies, which, however, resulted in a banking system that does not serve the needs of at least one-fifth of the population. In the euro area, the population has access to affordable financial services; however, neither the private nor the public sector has been able to provide the infrastructure to integrate European payments.
Promotion effect of FOXCUT as a microRNA sponge for miR-24-3p on progression in triple-negative breast cancer through the p38 MAPK signaling pathway
Authors: Yu Xiafei , Qian Fangze , Zhang Xiaoqiang , Zhu Yanhui , He Gao , Yang Junzhe , Wu Xian , Zhou Yi , Shen Li , Shi Xiaoyue , Zhang Hongfei , Liu Xiao'an
Published: January 2024

Background:

Triple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with a poor prognosis. According to new research, long noncoding RNAs (lncRNAs) play a significant role in the progression of cancer. Although the role of lncRNAs in breast cancer has been well reported, few studies have focused on TNBC. This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript (FOXCUT) in triple-negative breast cancer.

Methods:

Based on a bioinformatic analysis of the cancer genome atlas (TCGA) database, we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues, which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University. The functions of FOXCUT in proliferation, migration, and invasion were detected in vitro or in vivo. Luciferase assays and RNA immunoprecipitation (RIP) were performed to reveal that FOXCUT acted as a competitive endogenous RNA (ceRNA) for the microRNA miR-24-3p and consequently inhibited the degradation of p38.

Results:

lncRNA FOXCUT was markedly highly expressed in breast cancer, which was associated with poor prognosis in some cases. Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo. Mechanistically, FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38, which might act as an oncogene in breast cancer.

Conclusion:

Collectively, this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.
Effectiveness and safety of vedolizumab and infliximab in biologic-naive patients with Crohn’s disease: results from the EVOLVE study
Authors: Mantzaris Gerassimos J. , Bressler Brian , Adsul Shashi , Luo Michelle , Colby Chris , Brett Neil R. , Saha Sumit , Kamble Pravin , Wang Song , Yarur Andres
Published: January 2024

Objectives

This study compared the real-world effectiveness and safety of α4β7-integrin inhibitor vedolizumab and anti-tumor necrosis factor alpha (anti-TNFα) inhibitor infliximab in biologic-naive patients with Crohn’s disease (CD).

Methods

EVOLVE was a retrospective, multicenter, medical chart review of biologic-naive adults with inflammatory bowel disease receiving vedolizumab or anti-TNFα treatment as first-line biologics in Canada, Greece, and the USA. Twelve-month outcomes were analyzed in vedolizumab- or infliximab-treated patients with moderate-to-severe CD (and subgroups with complicated and noncomplicated CD) including cumulative rates of clinical response, clinical remission, and mucosal healing, and incidence rates of serious adverse events (SAEs) and serious infections (SIs). Inverse probability weighting (IPW) was used to account for baseline differences between treatment groups.

Results

Data were analyzed from 167 patients. In the IPW dataset (99 vedolizumab-treated and 63 infliximab-treated), adjusted 12-month clinical remission rates were 73.1% and 55.2%, respectively (P = 0.31). Overall, effectiveness rates were similar across treatment and complicated/noncomplicated disease subgroups. Adjusted 12-month incidence rates (first occurrence/1000 person-years) of SAEs for vedolizumab vs. infliximab: 43.6 vs. 200.9 [hazard ratio (HR) 0.36 (0.09–1.54)]; SIs: 10.8 vs. 96.0 [HR 0.08 (<0.01–2.64)]. AE incidence was significantly lower in vedolizumab- vs. infliximab-treated patients for complicated [131.6 vs. 732.2; HR 0.19 (0.05–0.65)] and noncomplicated [276.3 vs. 494.8; HR 0.59 (0.35–0.99)] disease subgroups.

Conclusion

These real-world data on first-line biologics show no differences in 12-month effectiveness outcomes for vedolizumab- vs. infliximab-treated biologic-naive patients with CD. Vedolizumab may have a more favorable safety profile vs. infliximab in patients with complicated and noncomplicated disease.
Anal defecatory function in ulcerative colitis patients after total proctocolectomy and ileal pouch-anal anastomosis: a prospective cohort study
Authors: Viazis Nikos , Manolakis Anastasios , Vraka Marina , Mylonas Iordanis , Tsoukali Emmanuela , Karamanolis George , Mantzaris Gerasimos J. , Papakonstantinou Ioannis
Published: January 2024

Background

Total proctocolectomy (TPC) followed by ileal pouch-anal anastomosis (IPAA) remains the only viable option whenever different treatment modalities fail in patients with ulcerative colitis (UC).

Objective

Prospective cohort pre/post study examining the anal defecatory function and competence in UC patients undergoing TPC plus IPAA using high-resolution anorectal manometry (HR-ARM).

Patients

Patients undergoing TPC and IPAA were enrolled in the study and subjected to HR-ARM prior to and 6 months after surgery. The anal resting, squeeze and push pressures were recorded, together with the rectal sensation and the rectal balloon expulsion test. The number of bowel movements, symptoms/signs related to fecal incontinence, as well as the IBDQ-32 quality of life questionnaires were documented during both HR-ARM visits.

Results

A total of 20 consecutive UC patients were recruited in our study. The mean (SD) number of bowel movements before the TPC plus IPAA was 10.1 (2.8), while the same number after the pouch surgery was 7.7 (3.1) [P = 0.01]. Symptoms or signs of fecal incontinence were noted in one of our patients prior to the operation; however, none of our patients reported any such symptoms after the pouch surgery. The median (IQR) IBDQ-32 questionnaire scores before and after surgery were 121.5 (13.5) and 142.5 (16.0) respectively. At the same time, the anorectal function remained intact since both the anal resting and squeeze pressures were not significantly changed.

Conclusion

UC patients subjected to TPC-IPAA exhibit improved bowel movements and a normal anal defecatory function and competence post-surgery.
Dendritic cell epithelial sodium channel induced inflammation and salt-sensitive hypertension
Authors: Demirci Mert , Hinton Antentor , Kirabo Annet
Published: January 2024

Purpose of review

Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular disease. Epithelial sodium channel (ENaC) plays a critical role in renal electrolyte and volume regulation and has been implicated in the pathogenesis of SSBP. This review describes recent advances regarding the role of ENaC-dependent inflammation in the development of SSBP.

Recent findings

We recently found that sodium enters dendritic cells via ENaC, a process regulated by serum/glucocorticoid-regulated kinase 1 and epoxyeicosatrienoic acid 14,15. Sodium entry activates NADPH oxidase, leading to the production of isolevuglandins (IsoLGs). IsoLGs adduct self-proteins to form neoantigens in dendritic cells that activate T cells and result in the release of cytokines promoting sodium retention, kidney damage, and endothelial dysfunction in SSBP. Additionally, we described a novel mechanistic pathway involving ENaC and IsoLG-dependent NLRP3 inflammasome activation. These findings hold promise for the development of novel diagnostic biomarkers and therapeutic options for SSBP.

The exact mechanisms underlying SSBP remain elusive. Recent advances in understanding the extrarenal role of ENaC have opened a new perspective, and further research efforts should focus on understanding the link between ENaC, inflammation, and SSBP.
COVID-19-related excess missed HIV diagnoses in the United States in 2021
Authors: Viguerie Alex , Song Ruiguang , Johnson Anna Satcher , Lyles Cynthia M. , Hernandez Angela , Farnham Paul G.
Published: January 2024

Objective:

Coronavirus disease 2019 (COVID-19) and related disruptions led to a significant decline in HIV diagnoses in the United States in 2020. A previous analysis estimated 18% fewer diagnoses than expected among persons with HIV (PWH) acquiring infection in 2019 or earlier, suggesting that the decline in overall diagnoses cannot be attributed solely to decreased transmission. This analysis evaluates the progress made towards closing the 2020 diagnosis deficit in 2021.

Methods:

We apply previously developed methods analyzing 2021 diagnosis data from the National HIV Surveillance System to determine whether 2021 diagnosis levels of PWH infected pre-2020 are above or below the expected pre-COVID trends. Results are stratified by assigned sex at birth, transmission group, geographic region, and race/ethnicity.

Results:

In 2021, HIV diagnoses returned to pre-COVID levels among all PWH acquiring infection 2011–2019. Among Hispanic/Latino PWH and male individuals, diagnoses returned to pre-COVID levels. White PWH, MSM, and PWH living in the south and northeast showed higher-than-expected levels of diagnosis in 2021. For the remaining populations, there were fewer HIV diagnoses in 2021 than expected.

Conclusion:

Although overall diagnoses among persons acquiring HIV pre-2020 returned to pre-COVID levels, the diagnosis gap observed in 2020 remained unclosed at the end of 2021. Fewer than expected diagnoses among certain populations indicate that COVID-19-related disruptions to HIV diagnosis trends remained in 2021. Although some groups showed higher-than-expected levels of diagnoses, such increases were smaller than corresponding 2020 decreases. Expanded testing programs designed to close these gaps are essential.
Differences in Breastfeeding Duration by Maternal HIV Status: A Pooled Analysis of Nationally Representative Surveys in Sub-Saharan Africa
Authors: Glaubius Robert , Stover John , Johnson Leigh F. , Mahiane Severin G. , Mahy Mary I. , Eaton Jeffrey W.
Published: January 2024

Background:

Breastfeeding improves child survival but is a source of mother-to-child HIV transmission among women with unsuppressed HIV infection. Estimated HIV incidence in children is sensitive to breastfeeding duration among mothers living with HIV (MLHIV). Breastfeeding duration may vary according to maternal HIV status.

Setting:

Sub-Saharan Africa.

Methods:

We analyzed pooled data from nationally representative household surveys conducted during 2003–2019 that included HIV testing and elicited breastfeeding practices. We fitted survival models of breastfeeding duration by country, year, and maternal HIV status for 4 sub-Saharan African regions (Eastern, Central, Southern, and Western).

Results:

Data were obtained from 65 surveys in 31 countries. In 2010, breastfeeding in the first month of life (“initial breastfeeding”) among MLHIV ranged from 69.1% (95% credible interval: 68–79.9) in Southern Africa to 93.4% (92.7–98.0) in Western Africa. Median breastfeeding duration among MLHIV was the shortest in Southern Africa at 15.6 (14.2–16.3) months and the longest in Eastern Africa at 22.0 (21.7–22.5) months. By comparison, HIV-negative mothers were more likely to breastfeed initially (91.0%–98.7% across regions) and for longer duration (median 18.3–24.6 months across regions). Initial breastfeeding and median breastfeeding duration decreased during 2005–2015 in most regions and did not increase in any region regardless of maternal HIV status.

Conclusions:

MLHIV in sub-Saharan Africa are less likely to breastfeed initially and stop breastfeeding sooner than HIV-negative mothers. Since 2020, UNAIDS-supported HIV estimates have accounted for this shorter breastfeeding exposure among HIV-exposed children. MLHIV need support to enable optimal breastfeeding practices and to adhere to antiretroviral therapy for HIV treatment and prevention of postnatal mother-to-child transmission.
Current challenges in acute bacterial skin infection management
Authors: Burillo Almudena , Pulido-Pérez Ana , Bouza Emilio
Published: January 2024

Purpose of review

There are aspects of skin and soft tissue infections (SSTIs) that remain unresolved, such as current numbers, classification criteria, how best to define severity and predict the outcome, what diagnostic tests to perform, what new treatment options are available, or what the duration of antibiotic treatment should be. We have reviewed the literature over the last 18 months to clarify these issues and provide our opinion.

Recent findings

SSTIs are common and among the top 10 most frequent infections worldwide. They represent a burden on the healthcare system and have a major impact on the quality of life of patients. Regarding classification, the Infectious Diseases Society of America (IDSA) provides a practical guide that distinguishes between uncomplicated and complicated infections, acute and chronic wound infections, and necrotising and nonnecrotizing infections based on skin extension and tissue necrosis. With new microbiological and imaging diagnostic techniques, SSTIs can now be better diagnosed. New PCR techniques are available, and mass spectrometry can be applied to samples collected in liquid transport media. Moreover, new treatment methods such as photodynamic therapy, reactive oxygen, and phages are emerging. SSTI patients can be treated with shorter antibiotic courses if they receive an active drug with good tissue penetration. Antibiotic treatment in necrotizing infections can be shortened to 48 h after the last debridement.

SSTIs remain a challenge regarding rapid and accurate diagnosis and clinical management.
NET-Induced Carcinoid Heart Disease Affecting Both Tricuspid and Aortic Valves Due to Patent Foramen Ovale and Right/Left Shunt
Authors: Laschinsky Christina , Welsner Matthias , Mahabadi Amir A. , Lahner Harald , Hautzel Hubertus
Published: January 2024

Carcinoid heart disease (Hedinger syndrome) is a long-term consequence in hormone-active neuroendocrine tumors with hepatic metastases and carcinoid syndrome. Because of serotonin, excess multiple cardiac and pulmonary symptoms evolve, which are further complicated by a patent foramen ovale due to right-left shunting. We present a 53-year-old man with an ileum-neuroendocrine tumor including gross liver metastases and long-term stable disease who subsequently developed Hedinger syndrome. Initially experiencing progressive dyspnea, he eventually experienced severe hypoxemia due to patent foramen ovale. 99mTc-MAA lung perfusion scintigraphy quantitatively identified the right-left shunting, whereas 68Ga-FAPI-46 PET/CT characterized the typical fibrous heart valve thickening due to serotonin-induced fibroblast proliferative properties.
Interictal Electrical Source Imaging
Authors: Rampp Stefan , Müller-Voggel Nadia , Hamer Hajo , Doerfler Arnd , Brandner Sebastian , Buchfelder Michael
Published: January 2024

Interictal electrical source imaging (ESI) determines the neuronal generators of epileptic activity in EEG occurring outside of seizures. It uses computational models to take anatomic and neuronal characteristics of the individual patient into account. The presented article provides an overview of application and clinical value of interictal ESI in patients with pharmacoresistant focal epilepsies undergoing evaluation for surgery. Neurophysiological constraints of interictal data are discussed and technical considerations are summarized. Typical indications are covered as well as issues of integration into clinical routine. Finally, an outlook on novel markers of epilepsy for interictal source analysis is presented. Interictal ESI provides diagnostic performance on par with other established methods, such as MRI, PET, or SPECT. Although its accuracy benefits from high-density recordings, it provides valuable information already when applied to EEG with only a limited number of electrodes with complete coverage. Novel oscillatory markers and the integration of frequency coupling and connectivity may further improve accuracy and efficiency.
Thyroid dysfunction and mortality in cardiovascular hospitalized patients
Authors: Frankel Meir , Bayya Feras , Munter Gabriel , Wolak Arik , Tolkin Lior , Barenhoz-Goultschin Orit , Asher Elad , Glikson Michael
Published: January 2024

Background

Thyroid dysfunction (TD) is associated with increased cardiovascular morbidity and mortality. Early detection may influence the clinical management.

Objective

To determine the prevalence, predictors, and prognostic value of TD among hospitalized cardiac patients.

Methods

A retrospective analysis of a 12-year database consisting of nonselectively adult patients admitted to a Cardiology Department and who were all screened for serum thyroid-stimulation-hormone (TSH) levels . Statistical analysis of demographic and clinical characteristics, mortality and length of hospital stay (LOS) was performed.

Results

A total of 14369 patients were included in the study; mean age was 67 years, 38.3% females. 1465 patients (10.2%) had TD. The most frequent type of TD was mildly elevated TSH (5.4%) followed by mildly reduced TSH (2.1%), markedly elevated TSH (1.5%), and markedly reduced TSH (1.2%). Female gender, history of hypothyroidism, heart failure, atrial fibrillation, renal failure and amiodarone use were significantly associated with TD. During follow-up 2975 (20.7%) patients died. There was increased mortality in the mildly reduced TSH subgroup (hazard ratio [HR] =1.44), markedly elevated TSH subgroup (HR=1.40) and mildly elevated TSH subgroup (HR=1.27). LOS was longer for patients with TD; the longest stay was observed in the markedly elevated TSH subgroup (odds ratio=1.69).

Conclusion

The prevalence of TD in hospitalized cardiac patients is 10.2%. TD is associated with an increased mortality rate and LOS. Consequently, routine screening for thyroid function in this population is advisable, particularly for selected high-risk subgroups. Future studies are needed to determine whether optimizing thyroid function can improve survival in these patients.
Postoperative Global Period Cost Reduction Using 3 Successive Risk-Stratified Pancreatectomy Clinical Pathways
Authors: Azimuddin Ahad , Tzeng Ching-Wei D , Prakash Laura R , Bruno Morgan L , Arvide Elsa M , Dewhurst Whitney L , Newhook Timothy E , Kim Michael P , Ikoma Naruhiko , Snyder Rebecca A , Lee Jeffrey E , Perrier Nancy D , Katz Matthew HG , Maxwell Jessica E
Published: January 2024

BACKGROUND:

We hypothesized that iterative revisions of our original 2016 risk-stratified pancreatectomy clinical pathways would be associated with decreased 90-day perioperative costs.

STUDY DESIGN:

From a single-institution retrospective cohort study of consecutive patients with 3 iterations: “version 1” (V1) (October 2016 to January 2019), V2 (February 2019 to October 2020), and V3 (November 2020 to February 2022), institutional data were aggregated using revenue codes and adjusted to constant 2022-dollar value. Grand total perioperative costs (primary endpoint) were the sum of pancreatectomy, inpatient care, readmission, and 90-day global outpatient care. Proprietary hospital-based costs were converted to ratios using the mean cost of all hospital operations as the denominator.

RESULTS:

Of 814 patients, pathway V1 included 363, V2 229, and V3 222 patients. Accordion Grade 3+ complications decreased with each iteration (V1: 28.4%, V2: 22.7%, and V3: 15.3%). Median length of stay decreased (V1: 6 days, interquartile range [IQR] 5 to 8; V2: 5 [IQR 4 to 6]; and V3: 5 [IQR 4 to 6]) without an increase in readmissions. Ninety-day global perioperative costs decreased by 32% (V1 cost ratio 12.6, V2 10.9, and V3 8.6). Reduction of the index hospitalization cost was associated with the greatest savings (−31%: 9.4, 8.3, and 6.5). Outpatient care costs decreased consistently (1.58, 1.41, and 1.04). When combining readmission and all outpatient costs, total “postdischarge” costs decreased (3.17, 2.59, and 2.13). Component costs of the index hospitalization that were associated with the greatest savings were room or board costs (−55%: 1.74, 1.14, and 0.79) and pharmacy costs (−61%: 2.20, 1.61, and 0.87; all p < 0.001).

CONCLUSIONS:

Three iterative risk-stratified pancreatectomy clinical pathway refinements were associated with a 32% global period cost savings, driven by reduced index hospitalization costs. This successful learning health system model could be externally validated at other institutions performing abdominal cancer surgery.
The best of both worlds: a proposal for further integration of Candidatus names into the International Code of Nomenclature of Prokaryotes
Authors: Arahal David , Bisgaard Magne , Christensen Henrik , Clermont Dominique , Dijkshoorn Lenie , Duim Birgitta , Emler Stefan , Figge Marian , Göker Markus , Moore Edward R. B. , Nemec Alexandr , Nørskov-Lauritsen Niels , Nübel Ulrich , On Stephen L. W. , Vandamme Peter , Ventosa Antonio
Published: January 2024

The naming of prokaryotes is governed by the International Code of Nomenclature of Prokaryotes (ICNP) and partially by the International Code of Nomenclature for Algae, Fungi and Plants (ICN). Such codes must be able to determine names of taxa in a universal and unambiguous manner, thus serving as a common language across different fields and activities. This unity is undermined when a new code of nomenclature emerges that overlaps in scope with an established, time-tested code and uses the same format of names but assigns different nomenclatural status values to the names. The resulting nomenclatural confusion is not beneficial to the wider scientific community. Such ambiguity is expected to result from the establishment of the ‘Code of Nomenclature of Prokaryotes Described from DNA Sequence Data’ (‘SeqCode’), which is in general and specific conflict with the ICNP and the ICN. Shortcomings in the interpretation of the ICNP may have exacerbated the incompatibility between the codes. It is reiterated as to why proposals to accept sequences as nomenclatural types of species and subspecies with validly published names, now implemented in the SeqCode, have not been implemented by the International Committee on Systematics of Prokaryotes (ICSP), which oversees the ICNP. The absence of certain regulations from the ICNP for the naming of as yet uncultivated prokaryotes is an acceptable scientific argument, although it does not justify the establishment of a separate code. Moreover, the proposals rejected by the ICSP are unnecessary to adequately regulate the naming of uncultivated prokaryotes. To provide a better service to the wider scientific community, an alternative proposal to emend the ICNP is presented, which would result in Candidatus names being regulated analogously to validly published names. This proposal is fully consistent with previous ICSP decisions, preserves the essential unity of nomenclature and avoids the expected nomenclatural confusion.
Talaromyces mellisjaponici sp. nov., a xerophilic species isolated from honey in Japan
Authors: Okubo Akari , Itagaki Tadashi , Hirose Dai
Published: January 2024

Five isolates of a xerophilic Talaromyces species were obtained from honey in Japan. Molecular phylogenetic analysis based on a combined dataset for four regions (rRNA internal transcribed spacer, β-tubulin, calmodulin and RNA polymerase II second largest subunit) revealed that the strains formed an independent clade in section Trachyspermi, which is sister to Talaromyces affinitatimellis, Talaromyces basipetosporus and Talaromyces speluncarum. The strains and their relatives have different growth on creatine agar, yeast extract sucrose agar and dichloran 18 % glycerol agar, different branching patterns (mostly monoverticillate or biverticillate, less frequently divaricate or terverticillate), and different sizes and surface structures of conidia. Xerotolerance tests were also conducted using media adjusted to five different sucrose concentrations (0, 20, 40, 60 and 80 %). The colony diameters of the strains were larger than those of T. affinitatimellis, T. basipetosporus and T. speluncarum at each sucrose concentration. Altogether, the obtained morphological, molecular and physiological data allowed the proposal of Talaromyces mellisjaponici sp. nov. for this novel species, with NBRC 116048T as the type strain.
Acidovorax benzenivorans sp. nov., a novel aromatic hydrocarbon-degrading bacterium isolated from a xylene-degrading enrichment culture
Authors: Bedics Anna , Táncsics András , Banerjee Sinchan , Tóth Erika , Harkai Péter , Gottschall Gerda Georgina , Bóka Károly , Kriszt Balázs
Published: January 2024

A Gram-stain-negative strain, designated as D2M1T was isolated from xylene-degrading enrichment culture and characterized using a polyphasic approach to determine its taxonomic position. The 16S rRNA gene sequence analysis revealed that strain D2M1T belongs to the genus

Acidovorax

, with the highest 16S rRNA gene similarity to

Acidovorax delafieldii

DSM 64T (99.93 %), followed by

Acidovorax radicis

DSM 23535T (98.77 %) and

Acidovorax kalamii

MTCC 12652T (98.76 %). The draft genome sequence of strain D2M1T is 5.49 Mb long, and the G+C content of the genome is 64.2 mol%. Orthologous average nucleotide identity and digital DNA–DNA hybridization relatedness values between strain D2M1T and its closest relatives were below the threshold values for species demarcation confirming that strain D2M1T is distinctly separated from its closest relatives. The whole genome analysis of the strain revealed a phenol degradation gene cluster, encoding a multicomponent phenol hydroxylase (mPH) together with a complete meta-cleavage pathway including an I.2.C-type catechol 2,3-dioxygenase (C23O) gene. The strain was able to degrade benzene and ethylbenzene as sole sources of carbon and energy under aerobic and microaerobic conditions. Cells were facultatively aerobic rods and motile with a single polar flagellum. The predominant fatty acids (>10 % of the total) of strain D2M1T were summed feature 3 (C16 : 1
 ω7c/C16 : 1
 ω6c), C16 : 0 and summed feature 8 (C18 : 1
 ω7c/C18 : 1
 ω6c). The major ubiquinone of strain D2M1T was Q8, while the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. Based on polyphasic data, it is concluded that strain D2M1T represents a novel species of the genus

Acidovorax

, for which the name of Acidovorax benzenivorans sp. nov. is proposed. The type strain of the species is strain D2M1T (=DSM 115238T=NCAIM B.02679T).
Local and systemic replicative fitness for viruses in specialist, generalist, and non-specialist interactions with salmonid hosts
Authors: Páez David J. , Kurath Gael , Powers Rachel L. , Naish Kerry A. , Purcell Maureen K.
Published: January 2024

Host tissues represent diverse resources or barriers for pathogen replicative fitness. We tested whether viruses in specialist, generalist, and non-specialist interactions replicate differently in local entry tissue (fin), and systemic target tissue (kidney) using infectious hematopoietic necrosis virus (IHNV) and three salmonid fish hosts. Virus tissue replication was host specific, but one feature was shared by specialists and the generalist which was uncommon in the non-specialist interactions: high host entry and replication capacity in the local tissue after contact. Moreover, specialists showed increased replication in systemic target tissues early after host contact. By comparing ancestral and derived IHNV viruses, we also characterized replication tradeoffs associated with specialist and generalist evolution. Compared with the ancestral virus, a derived specialist gained early local replicative fitness in the new host but lost replicative fitness in the ancestral host. By contrast, a derived generalist showed small replication losses relative to the ancestral virus in the ancestral host but increased early replication in the local tissue of novel hosts. This study shows that the mechanisms of specialism and generalism are host specific and that local and systemic replication can contribute differently to overall within host replicative fitness for specialist and generalist viruses.
Intraoperative Ablation Control Based on Real-time Necrosis Monitoring Feedback: Numerical Evaluation
Authors: Murakami Ryo , Mori Satoshi , Zhang Haichong K.
Published: January 2024

Ablation therapy is a type of minimally invasive treatment, utilized for various organs including the brain, heart, and kidneys. The accuracy of the ablation process is critically important to avoid both insufficient and excessive ablation, which may result in compromised efficacy or complications. The thermal ablation is formulated by two theoretical models: the heat transfer (HT) and necrosis formation (NF) models. In modern medical practices, feed-forward (FF) and temperature feedback (TFB) controls are primarily used as ablation control methodologies. FF involves pre-therapy procedure planning based on previous experiences and theoretical knowledge without monitoring the intraoperative tissue response, hence, it can’t compensate for discrepancies in the assumed HT or NF models. These discrepancies can arise due to individual patient’s tissue characteristic differences and specific environmental conditions. Conversely, TFB control is based on the intraoperative temperature profile. It estimates the resulting heat damage based on the monitored temperature distribution and assumed NF model. Therefore, TFB can make necessary adjustments even if there is an error in the assumed HT model. TFB is thus seen as a more robust control method against modeling errors in the HT model. Still, TFB is limited as it assumes a fixed NF model, irrespective of the patient or the ablation technique used. An ideal solution to these limitations would be to actively monitor heat damage to the tissue during the operation and utilize this data to control ablation. This strategy is defined as necrosis feedback (NFB) in this study. Such real-time necrosis monitoring modalities making NFB possible are emerging, however, there is an absence of a generalized study that discusses the integration and quantifies the significance of the real-time necrosis monitor techniques for ablation therapy. Such an investigation is expected to clarify the universal principles of how these techniques would improve ablation therapy. In this study, we examine the potential of NFB in suppressing errors associated with the NF model as NFB is theoretically capable of monitoring and suppressing the errors associated with the NF models in its closed control loop. We simulate and compare the performances of TFB and NFB with artificially generated modeling errors using the finite element method (FEM). The results show that NFB provides more accurate ablation control than TFB when NF-oriented errors are applied, indicating NFB’s potential to improve the ablation control accuracy and highlighting the value of the ongoing research to make real-time necrosis monitoring a clinically viable option.
Loss of dihydroceramide desaturase drives neurodegeneration by disrupting endoplasmic reticulum and lipid droplet homeostasis in glial cells
Authors: Zhu Yuqing , Cho Kevin , Lacin Haluk , Zhu Yi , DiPaola Jose T. , Wilson Beth A. , Patti Gary J. , Skeath James B.
Published: January 2024

Dihydroceramide desaturases convert dihydroceramides to ceramides, the precursors of all complex sphingolipids. Reduction of DEGS1 dihydroceramide desaturase function causes pediatric neurodegenerative disorder hypomyelinating leukodystrophy-18 (HLD-18). We discovered thatinfertile crescent (ifc), theDrosophila DEGS1homolog, is expressed primarily in glial cells to promote CNS development by guarding against neurodegeneration. Loss ofifccauses massive dihydroceramide accumulation and severe morphological defects in cortex glia, including endoplasmic reticulum (ER) expansion, failure of neuronal ensheathment, and lipid droplet depletion. RNAi knockdown of the upstream ceramide synthaseschlankin glia ofifcmutants rescues ER expansion, suggesting dihydroceramide accumulation in the ER drives this phenotype. RNAi knockdown ofifcin glia but not neurons drives neuronal cell death, suggesting thatifcfunction in glia promotes neuronal survival. Our work identifies glia as the primary site of disease progression in HLD-18 and may inform on juvenile forms of ALS, which also feature elevated dihydroceramide levels.
A Lipidomics Approach to Determine the Role of Lipids and its Crosstalk with Autophagy in Lung Cancer Metastasis
Authors: da Silva Rosa Simone C. , Alizadeh Javad , Vitorino Rui , Surendran Arun , Ravandi Amir , Kidane Biniam , Ghavami Saeid
Published: January 2024

Summary/Abstract

Non-small cell lung cancer (NSCLC) is among the most malignant tumors with high propensity for metastasis and is the leading cause of cancer-related death globally. Most patients present with regional and distant metastasis, associated with poor prognosis. Lipids may play an essential role in either activating or inhibiting detachment-induced apoptosis (anoikis), where the latter is a crucial mechanism to prevent metastasis, and it may have a cross-talk with autophagy. Autophagy has been shown to be induced in various human cancer metastasis, modulating tumor cell motility and invasion, cancer cell differentiation, resistance to anoikis, and epithelial to mesenchymal transition. Hence, it may play a crucial role in the transition of benign to malignant phenotypes, the core of metastasis initiation. Here, we provide a method we have established in our laboratory for detecting of lipids in attached and detached non-small lung cancer cells and show how to analyze lipidomics data to find its correlation with autophagy-related pathways.

Graphical abstract

Workflow of A549 attached and detached cell culture. Cells are collected, lipids are extracted and subjected to LC/MS processing. Next, lipidomics resulting data is analyzed through various steps involving utilization of Metaboanlyst, HDMB, Swiss Target Prediction, and String.
HortGenome Search Engine, a universal genomic search engine for horticultural crops
Authors: Wang Sen , Wei Shangxiao , Deng Yuling , Wu Shaoyuan , Peng Haixu , Qing You , Zhai Xuyang , Zhou Shijie , Li Jinrong , Li Hua , Feng Yijian , Yi Yating , Li Rui , Zhang Hui , Wang Yiding , Zhang Renlong , Ning Lu , Yao YunCong , Fei Zhangjun , Zheng Yi
Published: January 2024

Horticultural crops comprising fruit, vegetable, ornamental, beverage, medicinal and aromatic plants play essential roles in food security and human health, as well as landscaping. With the advances of sequencing technologies, genomes for hundreds of horticultural crops have been deciphered in recent years, providing a basis for understanding gene functions and regulatory networks and for the improvement of horticultural crops. However, these valuable genomic data are scattered in warehouses with various complex searching and displaying strategies, which increases learning and usage costs and makes comparative and functional genomic analyses across different horticultural crops very challenging. To this end, we have developed a lightweight universal search engine, HortGenome Search Engine (HSE;http://hort.moilab.net), which allows querying genes, functional annotations, protein domains, homologs, and other gene-related functional information of more than 400 horticultural crops. In addition, four commonly used tools, including ‘BLAST’, ‘Batch Query’, ‘Enrichment analysis’, and ‘Synteny Viewer’, have been developed for efficient mining and analysis of these genomic data.
Antigen non-specific CD8+T cells accelerate cognitive decline in aged mice following respiratory coronavirus infection
Authors: Reagin Katie L. , Lee Rae-Ling , Cocciolone Loren , Funk Kristen E.
Published: January 2024

Primarily a respiratory infection, numerous patients infected with SARS-CoV-2 present with neurologic symptoms, some continuing long after viral clearance as a persistent symptomatic phase termed “long COVID”. Advanced age increases the risk of severe disease, as well as incidence of long COVID. We hypothesized that perturbations in the aged immune response predispose elderly individuals to severe coronavirus infection and post-infectious sequelae. Using a murine model of respiratory coronavirus, mouse hepatitis virus strain A59 (MHV-A59), we found that aging increased clinical illness and lethality to MHV infection, with aged animals harboring increased virus in the brain during acute infection. This was coupled with an unexpected increase in activated CD8+T cells within the brains of aged animals but reduced antigen specificity of those CD8+T cells. Aged animals demonstrated spatial learning impairment following MHV infection, which correlated with increased neuronal cell death and reduced neuronal regeneration in aged hippocampus. Using primary cell culture, we demonstrated that activated CD8+T cells induce neuronal death, independent of antigen-specificity. Specifically, higher levels of CD8+T cell-derived IFN-γ correlated with neuronal death. These results support the evidence that CD8+T cells in the brain directly contribute to cognitive dysfunction following coronavirus infection in aged individuals.

eTOC summary

Using a murine model of respiratory coronavirus infection, we show that aging amplifies post-infectious cognitive dysfunction due to activated CD8+T cells that secrete IFN-γ in the brain. These data provide evidence that CD8+T cells in the brain negatively impact post-infectious cognitive function.
Nicotine enhances the stemness and tumorigenicity in intestinal stem cells via Hippo-YAP/TAZ and Notch signal pathway
Authors: Isotani Ryosuke , Igarashi Masaki , Miura Masaomi , Naruse Kyoko , Kuranami Satoshi , Katoh Manami , Nomura Seitaro , Yamauchi Toshimasa
Published: January 2024

Cigarette smoking is a well-known risk factor inducing the development and progression of various diseases. Nicotine (NIC) is the major constituent of cigarette smoke. However, knowledge of the mechanism underlying the NIC-regulated stem cell functions is limited. In this study, we demonstrate that NIC increases the abundance and proliferative activity of intestinal stem cells (ISCs) in vivo and ex vivo. Moreover, NIC induces Yes-associated protein (YAP) /Transcriptional coactivator with PDZ-binding motif (TAZ) and Notch signaling in ISCs via α7-nicotinic acetylcholine receptor (nAchR) and protein kinase C (PKC) activation; this effect was not detected in Paneth cells. The inhibition of Notch signaling by dibenzazepine (DBZ) nullified the effects of NIC on ISCs. NIC enhances in vivo tumor formation from ISCs after loss of the tumor suppressor gene Apc, DBZ inhibited NIC-induced tumor growth. Hence, this study identifies a NIC-triggered pathway regulating the stemness and tumorigenicity of ISCs and suggests the use of DBZ as a potential therapeutic strategy for treating intestinal tumors.
Integrated Analyses of Multi-omic Data Derived from Paired Primary Lung Cancer and Brain Metastasis Reveals the Metabolic Vulnerability as a Novel Therapeutic Target
Authors: Duan Hao , Ren Jianlan , Wei Shiyou , Li Chuan , Wang Zhenning , Li Meichen , Wei Zhi , Yang Zhenyu , Liu Yu , Xie Yuan , Wu Suwen , Hu Wanming , Guo Chengcheng , Zhang Xiangheng , Liang Lun , Yu Chengwei , Mou Yanhao , Jiang Yu , Li Houde , Sugarman Eric , Deek Rebecca A. , Chen Zexin , Chen Likun , Chen Yaohui , Yao Maojin , Liu Lunxu , Zhang Gao , Mou Yonggao
Published: January 2024

Lung cancer brain metastases (LC-BrMs) are frequently associated with dismal mortality rates in patients with lung cancer; however, standard of care therapies for LC-BrMs are still limited in their efficacy. A deep understanding of molecular mechanisms and tumor microenvironment of LC-BrMs will provide us with new insights into developing novel therapeutics for treating patients with LC-BrMs. Here, we performed integrated analyses of genomic, transcriptomic, proteomic and metabolomic data which were derived from a total number of 174 patients with paired and unpaired primary lung cancer and LC-BrM, spanning four published and two newly generated patient cohorts on both bulk and single cell levels. We uncovered that LC-BrMs exhibited significantly higher intra-tumor heterogeneity. We also observed that mutations in a subset of genes were almost always shared by both primary lung cancers and LC-BrM lesions, includingTTN, TP53, MUC16, LRP1B, RYR2, and EGFR. In addition, the genome-wide landscape of somatic copy number alterations was similar between primary lung cancers and LC-BrM lesions. Nevertheless, several regions of focal amplification were significantly enriched in LC-BrMs, including 5p15.33 and 20q13.33. Intriguingly, integrated analyses of transcriptomic, proteomic and metabolomic data revealed mitochondrial-specific metabolism was activated but tumor immune microenvironment was suppressed in LC-BrMs. Subsequently, we validated our results by conducting real-time quantitative reverse transcription PCR experiments, immunohistochemistry and multiplexed immunofluorescence staining of patients’ paired tumor specimens. Patients with a higher expression of mitochondrial metabolism genes but a lower expression of immune genes in their LC-BrM lesions tended to have a worse survival outcome. Therapeutically, targeting oxidative phosphorylation with gamitrinib in patient-derived organoids specific to LC-BrMs induced apoptosis and inhibited cell proliferation. The combination of gamitrinib plus anti-PD-1 immunotherapy significantly improved survival of mice bearing LC-BrMs. In conclusion, our findings not only provide comprehensive and integrated perspectives of molecular underpinnings of LC-BrMs but also contribute to the development of a potential, rationale-based combinatorial therapeutic strategy with the goal of translating it into clinical trials for patients with LC-BrMs.
Evolution of genetic (co)variances during the worldwide invasion ofDrosophila suzukii
Authors: Fraimout Antoine , Chantepie Stéphane , Navarro Nicolas , Teplitsky Céline , Debat Vincent
Published: January 2024

Biological invasions offer particularly convenient situations to study phenotypic evolution in natural populations. In particular, the comparison of derived, invasive populations with ancestral extant populations allows to investigate the relative impact of neutral demographic events, genetic constraints and selection on the evolution of phenotypes. In this paper, focusing on the worldwide invasion ofDrosophila suzukii(Matsumara, 1931), we investigate how phenotypic divergence among populations is constrained by the genetic correlations summarized in the genetic covariance matrixGand howGitself evolves throughout periods of drift and selection. Leveraging invasion history resolved by population genetics approaches, we compared wing shapeGmatrices among ancestral native and derived invasive populations, contrasting patterns of quantitative divergence among populations to neutral expectations. Our results show moderate yet significant quantitative genetic differentiation of wing shape amongD. suzukiipopulations and a relative stability in the structure ofG, presenting a roughly spherical shape but slightly different volumes. These characteristics likely reflect the demographic history of populations and suggest a low level of genetic constraint on adaptive evolution. The divergence among populations was greater than expected under a purely neutral model of evolution, compatible with an effect of selection on wing shape. Overall, our study suggests that selection, drift but not constraints affected the early stages of wing shape evolution duringD. suzukiiinvasion.
Rab10 regulates neuropeptide release by maintaining Ca2+homeostasis and protein synthesis
Authors: Dong Jian , Chen Miao , van Weering Jan R. T. , Li Ka Wan , Smit August B , Toonen Ruud F. , Verhage Matthijs
Published: January 2024

Dense core vesicles (DCVs) transport and release various neuropeptides and neurotrophins that control diverse brain functions, but the DCV secretory pathway remains poorly understood. Here, we tested a prediction emerging from invertebrate studies about the crucial role of the intracellular trafficking GTPase Rab10, by assessing DCV exocytosis at single-cell resolution upon acute Rab10 depletion in mature mouse hippocampal neurons, to circumvent potential confounding effects of Rab10’s established role in neurite outgrowth. We observed a significant inhibition of DCV exocytosis in Rab10-depleted neurons, whereas synaptic vesicle exocytosis was unaffected. However, rather than a direct involvement in DCV trafficking, this effect was attributed to two ER-dependent processes, ER-regulated intracellular Ca2+dynamics and protein synthesis. Gene ontology analysis of differentially expressed proteins upon Rab10 depletion identified substantial alterations in synaptic and ER/ribosomal proteins, including the Ca2+-pump SERCA2. In addition, ER morphology and dynamics were altered, ER Ca2+levels were depleted and Ca2+homeostasis was impaired in Rab10-depleted neurons. However, Ca2+entry using a Ca2+ionophore still triggered less DCV exocytosis. Instead, leucine supplementation, which enhances protein synthesis, largely rescued DCV exocytosis deficiency. We conclude that Rab10 is required for neuropeptide release by maintaining Ca2+dynamics and regulating protein synthesis. Furthermore, DCV exocytosis appeared more dependent on (acute) protein synthesis than synaptic vesicle exocytosis.