bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fumagillin inhibits growth of the enteric protozoan parasite
Entamoeba histolytica
by covalently binding to and selectively inhibiting methionine aminopeptidase 2
Authors: Watanabe Natsuki , Saito-Nakano Yumiko , Kurisawa Naoaki , Otomo Keisuke , Suenaga Kiyotake , Nakano Kentaro , Nozaki Tomoyoshi 
Published: October 2023

ABSTRACT

Amebiasis is an important cause of morbidity and mortality worldwide, and caused by infection with the protozoan parasite
Entamoeba histolytica
. Metronidazole is currently the first-line drug despite adverse effects and concerns on the emergence of drug resistance. Fumagillin, a fungal metabolite from
Aspergillus fumigatus,
and its structurally related natural and synthetic compounds have been previously explored as potential anti-angiogenesis inhibitors for cancers, anti-microbial, and anti-obese compounds. Although fumagillin was used for human amebiasis in clinical trials in 1950s, the mode of action of fumagillin remains elusive until now. In this report, we showed that fumagillin covalently binds to methionine aminopeptidase 2 (MetAP2) and non-covalently but abundantly binds to patatin family phospholipase A (PLA). Susceptibility against fumagillin of the amebic strains in which expression of
E. histolytica MetAP2
(
EhMetAP2
) gene was silenced increased compared to control strain. Conversely, overexpression of EhMetAP2 mutants that harbors amino acid substitutions responsible for resistance to ovalicin, a fumagillin analog, in human MetAP2, also resulted in decrease in fumagillin susceptibility. In contrast, neither gene silencing nor overexpression of
E. histolytica
PLA (EhPLA) affected fumagillin susceptibility. These data suggest that EhPLA is not essential and not the target of fumagillin for its amebicidal activity. Taken together, our data have demonstrated that EhMetAP2 is the primary target for amebicidal activity of fumagillin, and EhMetAP2 represents a rational explorable target for the development of alternative therapeutic agents against amebiasis.
Emergence of ciprofloxacin- and penicillin-resistant
Neisseria meningitidis
isolates in Japan between 2003 and 2020 and its genetic features
Authors: Takahashi Hideyuki , Morita Masatomo , Kamiya Hajime , Fukusumi Munehisa , Yasuda Mitsuru , Sunagawa Masatomi , Nakamura-Miwa Haruna , Ohama Yuki , Shimuta Ken , Ohnishi Makoto , Saito Ryoichi , Akeda Yukihiro 
Published: October 2023

ABSTRACT

Although we previously reported that some meningococcal isolates in Japan were resistant to penicillin (PCG) and ciprofloxacin (CIP), the antibiotic susceptibilities of
Neisseria meningitidis
isolates obtained in Japan remained unclear. In the present study, 290
N
.
meningitidis
isolates in Japan between 2003 and 2020 were examined for the sensitivities to eight antibiotics (azithromycin, ceftriaxone, ciprofloxacin, chloramphenicol, meropenem, minocycline, penicillin, and rifampicin). All isolates were susceptible to chloramphenicol, ceftriaxone, meropenem, minocycline, and rifampicin while two were resistant to azithromycin. Penicillin- and ciprofloxacin-resistant and -intermediate isolates (PCG
R
, CIP
R
, PCG
I
and CIP
I
, respectively) were also identified. Based on our previous findings from whole genome sequence analysis, approximately 40% of PCG
I
were associated with ST-11026 and cc2057 meningococci, both of which were unique to Japan. Moreover, the majority of ST-11026 meningococci were CIP
R
or CIP
I
. Sensitivities to PCG and CIP were closely associated with genetic features, which indicated that, at least for Japanese meningococcal isolates, PCG
R/I
or CIP
I/R
would be less likely to be horizontally conferred from other neisserial genomes by transferring of the genes responsible (
penA
and
gyrA
genes, respectively), but rather that ancestral
N. meningitidis
strains conferring PCG
R/I
or CIP
I/R
phenotypes clonally disseminated in Japan.
intI
1 gene abundance from septic tanks in Thailand using validated
intI
1 primers
Authors: Okonkwo Valentine , Cholet Fabien , Ijaz Umer Z. , Koottatep Thammarat , Pussayanavin Tatchai , Polpraset Chongrak , Sloan William T. , Connelly Stephanie , Smith Cindy J. 
Published: October 2023

ABSTRACT

Antimicrobial resistance (AMR) poses a serious global health threat, and wastewater treatment (WWT), including septic tanks, is a source of AMR. In Thailand, antibiotics are unregulated, and septic tanks are commonly used. Yet, their impact on the spread or mitigation of AMR is unknown. We monitored household and healthcare conventional septic tanks (CST) and household solar septic tanks (SST) in Thailand using the class 1 integron-integrase (
intI
1) gene abundance as a proxy for AMR. A systematic review of the literature found 65
intI
1 primers. We evaluated the coverage and specificity of each, including a new MGB TaqMan primer-probe, against clinical and environmental
intI
1,
intI
1-like, and non-
intI
1 databases. The three best primers were selected, laboratory validated for DNA and mRNA quantification, and used to quantify septic tank
intI
1 gene abundance. No primer set could distinguish between
intI
1 and
intI
1-like sequences. While primer choice did not affect gene abundance of the same sample (
P
-value > 0.05), sometimes when comparing the same samples quantified by different primers, statistical differences were observed for one but not the other primer set. This may lead to different interpretations of AMR risk. Irrespective of primers or reactor type
intI
1 gene abundance was greatest in influent > effluent > sludge.
intI
1 gene abundance was lowest in the effluent of the SST-household < CST-household < CST-healthcare. 31% to 42% of
intI
1 was removed by the CST-household tank, indicating while septic tanks remove some
intI
1 they remain a source to the surrounding environment. Toward the goal of achieving standardization across studies, we recommend the F3-R3 primer for
intI
1 quantification.

IMPORTANCE

Antimicrobial resistance is a global crisis, and wastewater treatment, including septic tanks, remains an important source of antimicrobial resistance (AMR) genes. The role of septic tanks in disseminating class 1 integron, and by extension AMR genes, in Thailand, where antibiotic use is unregulated remains understudied. We aimed to monitor gene abundance as a proxy to infer potential AMR from septic tanks in Thailand. We evaluated published
intI
1 primers due to the lack of consensus on optimal Q-PCR primers and the absence of standardization. Our findings confirmed septic tanks are a source of class 1 integron to the environment. We highlighted the significance of
intI
1 primer choice, in the context of interpretation of risk associated with AMR spread from septic tanks. We recommend the validated set (F3-R3) for optimal
intI
1 quantification toward the goal of achieving standardization across studies.
Multiple TonB homologs are important for carbohydrate utilization by
Bacteroides thetaiotaomicron
Authors: Pollet Rebecca M. , Foley Matthew H. , Kumar Supriya Suresh , Elmore Amanda , Jabara Nisrine T. , Venkatesh Sameeksha , Vasconcelos Pereira Gabriel , Martens Eric C. , Koropatkin Nicole M. 
Published: October 2023

ABSTRACT

The human gut microbiota is able to degrade otherwise undigestible polysaccharides, largely through the activity of
Bacteroides
. Uptake of polysaccharides into
Bacteroides
is controlled by TonB-dependent transporters (TBDTs), whose transport is energized by an inner membrane complex composed of the proteins TonB, ExbB, and ExbD.
Bacteroides thetaiotaomicron
(
B. theta
) encodes 11 TonB homologs that are predicted to be able to contact TBDTs to facilitate transport. However, it is not clear which TonBs are important for polysaccharide uptake. Using strains in which each of the 11 predicted
tonB
genes are deleted, we show that TonB4 (BT2059) is important but not essential for proper growth on starch. In the absence of TonB4, we observed an increase in the abundance of TonB6 (BT2762) in the membrane of
B. theta
, suggesting functional redundancy of these TonB proteins. The growth of the single deletion strains on pectic galactan, chondroitin sulfate, arabinan, and levan suggests a similar functional redundancy of the TonB proteins. A search for highly homologous proteins across other
Bacteroides
species and recent work in
Bacteroides fragilis
suggests that TonB4 is widely conserved and may play a common role in polysaccharide uptake. However, proteins similar to TonB6 are found only in
B. theta
and closely related species, suggesting that the functional redundancy of TonB4 and TonB6 may be limited across
Bacteroides
. This study extends our understanding of the protein network required for polysaccharide utilization in
B. theta
and highlights differences in TonB complexes across
Bacteroides
species.

IMPORTANCE

The human gut microbiota, including
Bacteroides
, is required for the degradation of otherwise undigestible polysaccharides. The gut microbiota uses polysaccharides as an energy source, and fermentation products such as short-chain fatty acids are beneficial to the human host. This use of polysaccharides is dependent on the proper pairing of a TonB protein with polysaccharide-specific TonB-dependent transporters; however, the formation of these protein complexes is poorly understood. In this study, we examine the role of 11 predicted TonB homologs in polysaccharide uptake. We show that two proteins, TonB4 and TonB6, may be functionally redundant. This may allow for the development of drugs targeting
Bacteroides
species containing only a TonB4 homolog with limited impact on species encoding the redundant TonB6.
Whole-genome sequence of the
Halobacillus naozhouensis
type strain KACC 21980
Authors: Choi Hyorim , Kim Seunghwan , Kim Yiseul , Heo Jun 
Published: October 2023

ABSTRACT

We present the whole-genome sequence of
Halobacillus naozhouensis
Korean Agricultural Culture Collection (KACC) 21980
T
, isolated from China by Chen et al.. The genome of
Halobacillus naozhouensis
KACC 21980
T
comprises a circular chromosome (4.2 Mb) and one plasmid (17 kb). It includes a total of 4,168 predicted coding genes.
Implementation factors influencing the sustained provision of tele-audiology services: insights from a combined methodology of scoping review and qualitative semistructured interviews
Authors: Ramkumar Vidya , Shankar Varsha , Kumar Shuba 
Published: October 2023

ObjectivesThe objectives of the current study were to (a) identify long-term tele-audiology services reported to be implemented beyond the research phase and determine whether they are sustained, (b) map the implementation process to Standards for Reporting Implementation Studies guidelines and (c) map the factors that influenced its sustainability to the Implementation Outcomes Framework (IOF) to understand the gaps from an implementation research perspective.Study design, setting and participantsThis cross-sectional study included a scoping review of articles describing long-term tele-audiology services from around the world to determine the factors influencing the implementation. Six electronic databases (PubMed, Cochrane Library, Web of Science, Scopus, Google Scholar and ProQuest) were searched for literature published between 2010 and 2023. This was followed by semistructured interviews (SSIs), which were guided by the IOF. Six project implementers were interviewed to obtain an in-depth understanding of factors that influenced sustainability of these tele-audiology services. Thematic analysis of the interview transcripts was carried out using a hybrid inductive-deductive approach.ResultsData were extracted from 32 tele-audiology studies included in the review, which were then mapped to 21 projects. The findings of the scoping review reveal that tele-audiology services were predominantly provided using synchronous telepractice methods. The ‘professional-facilitator-patient’ model was most commonly used. None of the studies reported the use of implementation research and/or outcome frameworks. Factors that influenced sustainability of tele-audiology services were identified from the combined results of the scoping review and the SSIs. These factors could be mapped to implementation outcomes of acceptability, adoption, feasibility, implementation cost and sustainability.ConclusionImplementation research and/or outcome framework should be used to guide the implementation processes, its evaluation and measurement of outcomes systematically in tele-audiology service delivery. When such frameworks are used, gaps in information regarding the context influencing implementation, reporting of fidelity and adaptability measures can be addressed.
Effect of long-term Tai Chi training on Parkinson’s disease: a 3.5-year follow-up cohort study
Authors: Li Gen , Huang Pei , Cui Shishuang , He Yachao , Tan Yuyan , Chen Shengdi 
Published: October 2023

BackgroundTai Chi has shown beneficial effects on the motor and non-motor symptoms of Parkinson’s disease (PD), but no study has reported the effect of long-term Tai Chi training.ObjectiveTo examine whether long-term Tai Chi training can maintain improvement in patients with PD.MethodsCohorts of patients with PD with Tai Chi training (n=143) and patients with PD without exercise as a control group (n=187) were built from January 2016. All subjects were assessed at baseline and in November 2019, October 2020 and June 2021. A logarithmic linear model was used to analyse rating scales for motor and non-motor symptoms. The need to increase antiparkinsonian therapies was presented as a Kaplan–Meier plot and as a box plot. The bootstrap method was used to resample for statistical estimation.ResultsTai Chi training reduced the annual changes in the deterioration of the Unified Parkinson’s Disease Rating Scale and delayed the need for increasing antiparkinsonian therapies. The annual increase in the levodopa equivalent daily dosage was significantly lower in the Tai Chi group. Moreover, patients benefited from Tai Chi training in motor symptoms, non-motor symptoms and complications.ConclusionTai Chi training has a long-term beneficial effect on PD, with an improvement in motor and non-motor symptoms and reduced complications.Trial registration numberNCT05447975.
Crop yields under no-till in Canada: implications for soil organic carbon change
Authors: VandenBygaart A.J. , Liang B.C. 
Published: October 2023

Crop yields directly affect carbon (C) inputs into soils. Tillage management can influence crop performance, and as such should be considered when quantifying soil organic carbon (SOC) change, and thus net greenhouse gas emissions from croplands for national greenhouse gas inventory reporting. We conducted a meta-analysis of the effects of no-tillage (NT) and conventional tillage (CT) on crop yields for multiple crop species, soil types, and climatic regions of Canada. Yield response to NT varied between western and eastern Canada. Regardless of crop type, experiment duration, soil texture, and residue management, experiments in eastern Canada showed an average of 6% lower yields ( p ≤ 0.005) under NT compared to CT. In western Canada, crop type had an important effect on yields between NT and CT with wheat, canola, and legumes exhibiting 10% ( p ≤ 0.001), 7% ( p ≤ 0.05), and 9% ( p ≤ 0.05) higher yields on average under NT compared to CT, respectively. In western Canada, higher yields would be reflected in a similar scale of higher C inputs to NT systems. A recent meta-analysis of the effects of tillage management on SOC in Canada showed an 8% higher storage of SOC under NT systems compared to CT, a difference limited to western Canadian soils. Incorporating the effect of tillage on C inputs will lead to improvements in the accuracy of the effects of tillage management on SOC change in Canadian cropland. The activity data can be improved by applying weightings to the yield data by site-specific assessment of tillage practices across Canada.
Neural network reconstruction of cosmology using the Pantheon compilation
Authors: Dialektopoulos Konstantinos F. , Mukherjee Purba , Said Jackson Levi , Mifsud Jurgen 
Published: October 2023

AbstractIn this work, we reconstruct the Hubble diagram using various data sets, including correlated ones, in artificial neural networks (ANN). Using ReFANN, that was built for data sets with independent uncertainties, we expand it to include non-Guassian data points, as well as data sets with covariance matrices among others. Furthermore, we compare our results with the existing ones derived from Gaussian processes and we also perform null tests in order to test the validity of the concordance model of cosmology.
Theoretical interpretation of the $$\Xi (1620)$$ and $$\Xi (1690)$$ resonances seen in $$\Xi _c^+ \rightarrow \Xi ^- \pi ^+ \pi ^+$$ decay
Authors: Li Hai-Peng , Zhang Gong-Jie , Liang Wei-Hong , Oset E. 
Published: October 2023

AbstractWe study the Belle reaction $$\Xi _c^+ \rightarrow \Xi ^- \pi ^+ \pi ^+$$

Ξ
c
+

→

Ξ
-

π
+

π
+

looking at the mass distribution of $$\pi ^+ \Xi $$

π
+

Ξ

, where clear signals for the $$\Xi (1620)$$

Ξ
(
1620
)

and $$\Xi (1690)$$

Ξ
(
1690
)

resonances are seen. These two resonances are generated dynamically from the interaction in coupled channels of $$\pi \Xi , {\bar{K}} \Lambda , {\bar{K}} \Sigma $$

π
Ξ
,

K

¯

Λ
,

K

¯

Σ

and $$\eta \Xi $$

η
Ξ

within the chiral unitary approach. Yet, the weak decay process at the quark level, together with the hadronization to produce pairs of mesons, does not produce the $$\pi \pi \Xi $$

π
π
Ξ

final state. In order to produce this state one must make transitions from the $${\bar{K}} \Lambda , {\bar{K}} \Sigma $$

K

¯

Λ
,

K

¯

Σ

and $$\eta \Xi $$

η
Ξ

components to $$\pi \Xi $$

π
Ξ

, and this interaction is what produces the resonances. So, the reaction offers a good test for the molecular picture of these resonances. Adding the contribution of the $$\Xi ^*(1530)$$

Ξ
∗

(
1530
)

and some background we are able to get a good reproduction of the mass distribution showing the signatures of the two resonances as found in the experiment.
Targeted Degradation of XIAP is Sufficient and Specific to Induce Apoptosis in MYCN-overexpressing High-risk Neuroblastoma
Authors: Choo Zhang'E , Koh Xiaoying , Wong Megan Rui En , Ashokan Ruth Minothini , Ali Ahamed Nurul Suhana Binte , Kang CongBao , Kuick Chik Hong , Chang Kenneth Tou En , Larisch Sarit , Loh Amos Hong Pheng , Chen Zhi Xiong 
Published: October 2023

Abstract

XIAP, the most potent mammalian inhibitor of apoptosis protein (IAP), critically restricts developmental culling of sympathetic neuronal progenitors, and is correspondingly overexpressed in most MYCN-amplified neuroblastoma tumors. Because apoptosis-related protein in the TGFβ signaling pathway (ARTS) is the only XIAP antagonist that directly binds and degrades XIAP, we evaluated the preclinical effectiveness and tolerability of XIAP antagonism as a novel targeting strategy for neuroblastoma. We found that antagonism of XIAP, but not other IAPs, triggered apoptotic death in neuroblastoma cells. XIAP silencing induced apoptosis while overexpression conferred protection from drug-induced apoptosis. From a screen of IAP inhibitors, first-in-class ARTS mimetic A4 was most effective against high-risk and high XIAP-expressing neuroblastoma cells, and least toxic toward normal liver- and bone marrow–derived cells, compared with pan-IAP antagonists. On target engagement assays and nuclear magnetic resonance spectroscopy, A4 was observed to degrade rather than inhibit XIAP, catalyzing rapid degradation of XIAP through the ubiquitin-proteasome pathway. In MYCN-amplified neuroblastoma patient-derived xenografts, A4 significantly prolonged survival as a single agent, and demonstrated synergism with standard-of-care agents to reduce their effective required doses 3- to 6-fold. Engagement and degradation of XIAP by ARTS mimetics is a novel targeting strategy for neuroblastoma that may be especially effective against MYCN-amplified disease with intrinsically high XIAP expression. First-in-class ARTS mimetic A4 demonstrates preclinical efficacy and warrants further development and study.

Significance:
XIAP degradation is sufficient to kill MYCN-amplified neuroblastoma which overexpresses and relies on XIAP as a brake against cell death, without affecting normal cells.
The effects of climate change awareness on mental health: Comparison of climate anxiety and hopelessness levels in Turkish youth
Authors: Ediz Çiçek , Yanik Derya 
Published: October 2023

Background: Climate anxiety, one of the negative emotions created by climate change, is particularly prevalent among climate activists and young individuals who hold a more serious concern for environmental issues. Aim: This study aims to determine the effects of climate change awareness on the mental health of young people in Turkey. Methods: Designed as a descriptive and two-group comparative study, the target population of this study comprises young individuals aged 15 to 24 who are climate activists and those who are not. The study data was collected through e-questionnaires administered between March 15 and May 10, 2023, using a demographic characteristics form, a climate change anxiety scale and the Beck Hopelessness Scale. The study was completed with a total of 306 participants, including 103 young individuals who are climate activists and 203 young individuals who are not climate activists. Results: We determined that young individuals who are climate activists have a high level of climate change anxiety, while those who are not climate activists have a moderate level of climate change anxiety. We found that the levels of hopelessness in both groups are at a mild level. Additionally, within the group of climate activists, we observed that individuals with a higher level of knowledge about climate change tend to exhibit greater levels of hopelessness. Conclusions: We identified that as awareness and knowledge about climate change increase, climate change anxiety, and hopelessness also increase. There is a need for studies to determine youth-specific mental health interventions to address mental health issues related to climate change awareness.
Cultural competence of mental health practitioners in the Netherlands
Authors: Hoshmand S , Knegtering H , Spoelstra SK 
Published: October 2023

Background: The importance of providing mental health from a transcultural perspective in establishing a therapeutic alliance is recognized. However, it is currently unknown how many mental health practitioners in the Netherlands feel capable of providing mental healthcare from a transcultural perspective, or if they are familiar with the Cultural Formulation Interview (CFI). The CFI is a tool used in mental health care to gather culturally relevant patient information, enhancing cultural sensitivity in treatment. It is also unknown if there is a difference between psychiatrist and psychiatry residents in terms of their cultural competence. Aims: This study aimed to assess the self-appraised cultural competence of Dutch psychiatrist and psychiatry residents, including their knowledge of the CFI, and the need for further training. Methods: A cross-sectional study was conducted among psychiatrists and psychiatry residents by means of an online questionnaire. Results: Ninety-seven mental health practitioners completed the questionnaire. Of the psychiatrists 70% and of the residents 76% reported that treating patients from cultural backgrounds different from their own background is challenging. Only 44% of psychiatrists and 34% of residents considered themselves sufficiently culturally competent, and 56% and 47% respectively, were uninformed about the CFI. The majority of psychiatrists and residents (70 vs 84%) indicated a need for more training in cultural competence. Conclusion: The majority of psychiatrists and residents in The Netherlands considered treating patients from different cultural backgrounds a challenge, reported feeling insufficiently culturally competent, lacked experience with the cultural formulation interview and reported a need for more training in cultural competence.