bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world study of trastuzumab and pertuzumab combined with chemotherapy in neoadjuvant treatment for patients with HER2-positive breast cancer
Authors: Ma Xiangmin , Zhang Xiangmei , Zhou Xinping , Ren Xiaofei , Ma Xindi , Zhang Weifang , Yang Ruiling , Song Tao , Liu Yunjiang 
Published: October 2022

Clinical trials have shown that trastuzumab (H) and pertuzumab (P) combined with chemotherapy as neoadjuvant therapy increased pathological complete response (pCR) rate of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, date in China in the real world are currently limited.
Clinical data from patients with HER2-positive breast cancer who received HP combined with chemotherapy as neoadjuvant therapy at 2 institutions from March 2019 to February 2022 were retrospectively analyzed. Adverse reactions were evaluated using CTCAE version 5.0. The primary endpoint was total pathologic complete response (tpCR; ypT0/isypN0), and the secondary endpoints were breast pathologic complete response (bpCR; ypT0/is) and axillary pathologic complete response (apCR; ypN0). Factors influencing tpCR were also analyzed.
A total of 302 patients were included in the analysis, of which 145 were treated with H + P + taxane + carboplatin (TcbHP), 94 with H + P + taxane (THP) and 63 with sequential anthracycline and cyclophosphamide, followed by H + P + taxane (AC-THP). The overall tpCR rate was 64.9%, and those of TcbHP, THP, and AC-THP were 73.1%, 52.1%, and 65.1%, respectively. The tpCR rate of the hormone receptor (HR) negative group (80.3%) was higher than that of the HR positive group (52.1%). The overall bpCR rate was 73.5% and the apCR rate was 75.8%. In the univariate analysis, HR, HER2 status and treatment regimen were related factors that affected tpCR. In the multivariate analysis, HR, HER2 status and treatment regimen were independent predictors of tpCR (P < .001, P < .001 and P = .009). The levels 3 and 4 toxicities rates of TcbHP were slightly higher than those of THP and AC-THP.
HP combined with chemotherapy has achieved a high pCR rate. The TcbHP regimen had the highest pCR. HR-negative tumors demonstrated a higher pCR. HR, HER2 status and treatment regimen were independent predictors of tpCR. The adverse reactions are controllable.
Probiotics and rifaximin for the prevention of travelers’ diarrhea: A systematic review and network meta-analysis
Authors: Fan Hao , Gao Lei , Yin Zidan , Ye Sheng , Zhao Hua , Peng Qi 
Published: October 2022

Background:
Probiotics and rifaximin are treatments for gut microbiota dysbiosis in patients with traveler’s diarrhea (TD), and they both proved beneficial for the prevention of TD. However, comparative effectiveness research between them has not been performed. A systematic review and network meta-analysis are to be performed to clarify which of them is more effective in the prevention of TD.

Methods:
Literature concerning the effectiveness of probiotics or rifaximin in the prevention of TD was searched in Medline, Embase, the Cochrane Central Register of Controlled Trials, and clinical registries for randomized controlled trials (RCTs) from inception of these databases to November 30, 2021 without any language restrictions. The primary efficacy outcome was the incidence of TD, and the safety outcome was the incidence of adverse events. The effect size of probiotics was measured by using relative ratio (RR), and the network meta-analysis was performed by using a frequentist approach and a random-effect model.

Results:
Totally 17 RCTs after screening 1119 retrieved records were included in analysis and 9 RCTs were with low risk of bias. Compared with placebo, both probiotics and rifaximin were associated with lower incidence of TD (probiotics, RR 0.85, 95% CI 0.76–0.95; rifaximin, RR 0.47, 95% CI 0.35–0.63), and rifaximin was more effective than probiotics (RR 0.56, 95% CI 0.4–0.78). Further analysis showed that sodium butyrate, rifaximin and L. acidophilus + L. bulgaricus + Bifido.bifidum + Strept. Thermophilus were the three most effective treatments for TD.

Conclusions:
Both rifaximin and probiotics are superior over placebo, and rifaximin has better treatment effect than probiotics in reducing the incidence of TD. Different types of probiotics have heterogeneous treatment effects.
Population-Level Provider Compliance With Provincial Treatment Guidelines for the Management of Gonorrhea in Adolescents and Adults in Alberta, Canada; 2000 to 2019
Authors: Ugarte-Torres Alejandra , Diaz Pallares Carolina , Niruban John S. , Smyczek Petra , Gratrix Jennifer , Strong David , Singh Ameeta E. 
Published: October 2022

Background
Appropriate antimicrobial therapy is one of the essential strategies in the global control of gonorrhea. We sought to determine the provider compliance with provincial treatment guidelines for gonococcal infections in Alberta, Canada, and to identify characteristics associated with provider noncompliance.

Methods
A retrospective population-based analysis of gonorrhea treatment from January 1, 2000, to December 31, 2019, using data extracted from a communicable disease database was performed. Prevalence ratios were calculated for provider compliance to treatment guidelines of patient, infection, and treating provider characteristics.

Results
We identified a total of 42,875 cases of gonorrhea, 58.3% were men, 40.3% were White, 28.2% were First Nations, and 16% were “unknown ethnicity.” Most cases were treated by family physicians (43.4%), sexually transmitted infection (STI) clinics (31.9%) and urgent care centers/hospitals (10%). Overall, there was 80.3% provider compliance with treatment guidelines. Provider compliance to treatment guidelines had the highest rates of compliance when treatment was provided by STI nurses in correctional facilities, STI clinics, and treatment of men having sex with men (94.7%, 91.7%, and 87.5%, respectively). Provider compliance to treatment guidelines was lowest when treating women (75.5%), pregnancy status (68.4), individuals of “unknown race/ethnicity” (74.8%), and those treated in urgent care centers and emergency department (66.7%).

Conclusions
Delivery of STI care by nurse-led models had the highest level of compliance with treatment guidelines. Our study informs areas for targeted interventions to improve the uptake of treatment guidelines, including the provision of treatment in urgent care centers and among women.
Signaling pathways involved in the repression of root nitrate uptake by nitrate inArabidopsis thaliana
Authors: Chaput Valentin , Li Jianfu , Séré David , Tillard Pascal , Fizames Cécile , Moyano Tomas , Zuo Kaijing , Martin Antoine , Gutiérrez Rodrigo A. , Gojon Alain , Lejay Laurence 
Published: October 2022

AbstractInArabidopsis thaliana, root high-affinity nitrate (NO3-) uptake depends mainly on NRT2.1, 2.4 and 2.5, which are repressed by high NO3-supply at the transcript level. ForNRT2.1, this regulation is due to the action of (i) feedback downregulation by N metabolites and (ii) repression by NO3-itself mediated by the transceptor NRT1.1(NPF6.3). However, forNRT2.4andNRT2.5the signaling pathway(s) remain unknown along with the molecular elements involved. Here we show that unlikeNRT2.1, NRT2.4andNRT2.5are not induced in a NO3-reductase mutant but are strongly upregulated following replacement of NO3-by ammonium (NH4+) as the N source. Moreover, increasing NO3-concentration in a mixed nutrient solution with constant NH4+concentration results in a gradual repression ofNRT2.4andNRT2.5, which is suppressed in anrt1.1mutant. This indicates thatNRT2.4andNRT2.5are subjected to repression by NRT1.1-mediated NO3-sensing, and not to feedback repression by reduced N metabolites. We further show that key regulators of NRT2s transporters, such as HHO1, HRS1, PP2C, LBD39, BT1 and BT2, are also regulated by NRT1.1-mediated NO3-sensing, and that several are involved in NO3-repression ofNRT2.1, 2.4and2.5. Finally, we provide evidence that it is the phosphorylated form of NRT1.1 at the T101 residue, which is most active in triggering the NRT1.1-mediated NO3-regulation of all these genes. Altogether, these data led to propose a regulatory model for high-affinity NO3-uptake inArabidopsis, highlighting several NO3-transduction cascades downstream the phosphorylated form of the NRT1.1 transceptor.One sentence summaryCharacterisation and identification of molecular elements involved in the signaling pathways repressing NRT2s transporters and root nitrate uptake in response to nitrate.
High nucleotide diversity accompanies differential DNA methylation in naturally diverging populations
Authors: Ord James , Gossmann Toni I. , Adrian-Kalchhauser Irene 
Published: October 2022

AbstractEpigenetic mechanisms such as DNA methylation (DNAme) are thought to comprise an invaluable adaptive toolkit in the early stages of local adaptation, especially when genetic diversity is constrained. However, the link between genetic diversity and DNAme has been scarcely examined in natural populations, despite its potential to shed light on the evolutionary forces acting on methylation state. Here, we analysed reduced-representation bisulfite sequencing and whole genome pool-seq data from marine and freshwater stickleback populations to examine the relationship between DNAme variation (between- and within-population), and nucleotide diversity in the context of freshwater adaptation. We find that sites that are differentially methylated between populations have higher underlying standing genetic variation, with diversity higher among sites that gained methylation in freshwater than those that lost it. Strikingly, while nucleotide diversity is generally lower in the freshwater population as expected from a population bottleneck, this is not the case for sites which lost methylation which instead have elevated nucleotide diversity in freshwater compared to marine. Subsequently, we show that nucleotide diversity is higher among sites with ancestrally variable methylation and also positively correlates with the sensitivity to environmentally induced methylation change. Both suggest that as selection on the control of methylation state becomes relaxed, so too does selection against mutations at the sites themselves. Increased epigenetic variance in a population is therefore likely to precede genetic diversification.
Development and validation of a type 2 diabetes machine learning classification model for EHR-based diagnostics and clinical decision support
Authors: Glanz Victor , Dudenkov Vladimir , Velikorodny Alexey 
Published: October 2022

AbstractBackgroundUndiagnosed type 2 diabetes continues to represent a significant challenge for all national healthcare systems. Although diagnostic criteria and laboratory screening procedures are well-established, clinical tests have limitations, and in many cases, diagnosis confirmation and more accurate interpretation of the test results are required. Machine learning methods, when applied to clinical outcome risk prediction, demonstrate great effectiveness, as they recognize specific patterns in data dynamics and thus can be used for the identification of at-risk cases where diabetes and complications can be delayed or even prevented. The aim of this study was to develop a type 2 diabetes machine learning model capable of efficient early identification of diabetes presence based on the results of common laboratory tests.MethodsReal-world medical data from electronic medical records were subjected to a multistage processing, including feature selection, missing values imputation. The machine learning algorithms adopted in this study were XGBoost, multilayer perceptron, ridge classifier, ridge classifier with polynomial features, bootstrap aggregating, dynamic ensemble selection, stacked generalization. An external dataset was analyzed via the same workflow to validate the initial results. The study was designed in accordance with the TRIPOD statement.ResultsWe have developed a machine learning classification model for type 2 diabetes that possesses several important advantages over conventional clinical methods (specifically, FINDRISC, ADA risk score). Performance metrics for the diabetes diagnostic model were 0.96 AUC, 92% specificity, and 89% sensitivity (mean values).ConclusionsThe study results potentially have major clinical implication and provide a contribution to the field of conventional diabetes risk assessment tools. Being specifically trained on real-world laboratory data and based on satisfactory external validation results, the present diagnostic type 2 diabetes model demonstrates high generalizability and can serve as a medical decision support and health monitoring tool.
Progressive spread of chromosomal inversions blends the role of colonization and evolution in a parallel Galápagos beetle radiation
Authors: Vangestel Carl , De Corte Zoë , Van Belleghem Steven M. , Vandekerckhove Matthias , Gharbi Karim , Hendrickx Frederik 
Published: October 2022

AbstractArchipelago island fauna include some of the most compelling examples of parallel adaptation to ecological gradients. However, despite the insuslar nature of these systems, the possibility that repeated instances of within-island divergence resulted from independent (in situ) evolutionary rather than repeated colonization events remains most often unclear. Here, we investigated the genomic underpinning of a progressive adaptive radiation of caterpillar-hunter beetles (Calosoma) in the low- and highland habitats from the Galápagos. TheseCalosomabeetles have evolved only partially reduced wings in the highland of the youngest islands but evolved to distinct short-winged species in the highland of the oldest islands. In support of independent evolutionary events, the extent of genome-wide divergence between long-winged lowland and short-winged highland populations decreased towards younger islands. However, in support of repeated colonization events, adaptation to highland habitats was driven by repeated selection of alleles that are shared across all highland species and populations. These alleles comprised extensive chromosomal inversions whose origin was traced back to an initial high-lowland divergence event on the oldest island. Moreover, we found evidence that after this initial divergence event, highland alleles spread to younger islands through dispersal of highland individuals as well as dispersal of lowland individuals that were polymorphic at adaptive loci, both providing the opportunity for the establishment of highland populations on the younger islands. These findings highlight the importance of an old divergence in driving repeated adaptation to ecological gradients. Complex histories of colonization and introgression may thus result in a mixed contribution of inter-island dispersal and within-island evolution in shaping parallel species communities on islands.
Computational constraints on the associative recall of spatial scenes
Authors: Ryom Kwang Il , Stendardi Debora , Ciaramelli Elisa , Treves Alessandro 
Published: October 2022

AbstractWe consider a model of associative storage and retrieval of compositional memories in an extended cortical network. Our model network is comprised of Potts units, which represent patches of cortex, interacting through long-range connections. The critical assumption is that a memory is composed of a limited number of items, each of which has a pre-established representation: storing a new memory only involves acquiring the connections, if novel, among the participating items. The model is shown to have a much lower storage capacity than when it stores simple unitary representations. It is also shown that an input from the hippocampus facilitates associative retrieval. When it is absent, it is advantageous to cue rare rather than frequent items. The implications of these results for emerging trends in empirical research are discussed.
Cohort Profile: The Danish National Cohort Study of Effectiveness and Safety of SARS-CoV-2 vaccines (ENFORCE)
Authors: Stærke Nina Breinholt , Reekie Joanne , Johansen Isik S. , Nielsen Henrik , Benfield Thomas , Wiese Lothar , Søgaard Ole Schmeltz , Tolstrup Martin , Iversen Kasper Karmark , Tarp Britta , Larsen Fredrikke Dam , Larsen Lykke , Lindvig Susan Olaf , Holden Inge Kristine , Iversen Mette Brouw , Knudsen Lene Surland , Fogh Kamille , Jakobsen Marie Louise , Traytel Anna , Østergaard Lars , Lundgren Jens ,   the ENFORCE Study Group
Published: October 2022

AbstractPurposeThe ENFORCE cohort is a national Danish prospective cohort of adults who received a Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine as part of the Danish National SARS-CoV-2 vaccination program. It was designed to investigate the long-term effectiveness, safety and durability of SARS-CoV-2 vaccines used in Denmark.ParticipantsA total of 6943 adults scheduled to receive a SARS-CoV-2 vaccine in the Danish COVID-19 Vaccination Program were enrolled in the study prior to their first vaccination. Participants will be followed for a total of two years with five predetermined follow-up visits and additional visits in relation to any booster vaccination. Serology measurements are performed after each study visit. T-cell immunity is evaluated at each study visit for a subgroup of 699 participants. Safety information is collected from participants at visits following each vaccination. Data on hospital admissions, diagnoses, deaths and SARS-CoV-2 polymerase chain reaction (PCR) results are collected from national registries throughout the study period. The median age of participants was 64 years (IQR 53-75), 56.6% were females and 23% were individuals with an increased risk of a serious course of COVID-19. A total of 340 (4.9%) participants tested positive for SARS-CoV-2 spike IgG at baseline.Findings to dateResults have been published on risk factors for humoral hyporesponsiveness and non-durable response to SARS-CoV-2 vaccination, the risk of breakthrough infections at different levels of SARS-CoV-2 spike IgG by viral variant, and on the antibody neutralizing capacity against different SARS-CoV-2 variants following primary and booster vaccinations.Future plansThe ENFORCE cohort will continuously generate studies investigating immunological response, effectiveness, safety and durability of the SARS-CoV-2 vaccines.Registrationclinicaltrials.govidentifier:NCT04760132.Strengths and limitations- The ENFORCE study combines repeated detailed SARS-CoV-2 specific immunological measurements prior to, and throughout the course of SARS-CoV-2 vaccination, with register-based follow-up of safety data and microbiological test results.- The ENFORCE cohort includes a large proportion of elderly participants and participants with concomitant diseases.- The three vaccine groups display a high degree of variation in demographic factors and distribution across risk groups, due to the prioritization of specific vaccines to risk groups during the primary roll out of the SARS-CoV-2 vaccination program.
Proteomics of resilience to Alzheimer’s disease identifies brain regional soluble Aβ levels, actin filament processes, and response to injury
Authors: Huang Zhi , Merrihew Gennifer E. , Larson Eric B. , Park Jea , Plubell Deanna , Fox Edward J. , Montine Kathleen S. , Keene C. Dirk , Zou James Y. , MacCoss Michael J. , Montine Thomas J. 
Published: October 2022

AbstractResilience to Alzheimer’s disease (RAD) is an uncommon combination of high disease burden without dementia that may provide critical insights into limiting the clinical impact of this incurable disease. In this study, we used mass spectrometry-based proteomics to quantify regional protein differences that characterize RAD. Starting with over 700 brain donations, we identified 43 extensively annotated research participants who met stringent inclusion exclusion criteria and analyzed matched isocortical regions, hippocampus, and caudate nucleus. Differential expression analysis of 7,115 soluble proteins identified lower isocortical and hippocampal soluble Aβ peptide levels as a significant feature of RAD. Protein co-expression analysis revealed a group of 181 densely-interacting proteins significantly associated with RAD that were enriched for actin filament-based process, cellular detoxification, and wound healing in isocortex and hippocampus. We further support our findings using data from 689 human isocortical samples from four independent external cohorts that were the closest approximations of our clinico-pathologic groups. The molecular basis of RAD, a widely replicated state in older adults for which there is no experimental model, likely holds important insights into therapeutic interventions for Alzheimer’s disease.
Scaling patterns of body plans differ among squirrel ecotypes
Authors: Linden Tate J. , Burtner Abigail E. , Rickman Johannah , McFeely Annika , Santana Sharlene E. , Law Chris J. 
Published: October 2022

AbstractBody size is often hypothesized to facilitate or constrain morphological diversity in the cranial, appendicular, and axial skeletons. However, how overall body shape scales with body size (i.e., body shape allometry) and whether these scaling patterns differ between ecological groups remains poorly investigated. Here, we test whether and how the relationships between body shape, body size, and limb lengths differ among species with different locomotory specializations, and describe the underlying morphological components that contribute to body shape variation among squirrel (Sciuridae) ecotypes. We quantified the body size and shape of 87 squirrel species from osteological specimens held at museum collections. Using phylogenetic comparative methods on these data, we found that 1) body shape and its underlying morphological components scale allometrically with body size, but these allometric patterns differ among squirrel ecotypes; 2) only ground squirrels exhibit a relationship between forelimb length and body shape, where more elongate species exhibit relatively shorter forelimbs; and 3) the relative length of the ribs and elongation or shortening of the thoracic region contributes the most to body shape variation across squirrels. Overall, our work contributes to the growing understanding of mammalian body shape evolution and how it is influenced by body size and locomotor ecology, in this case from robust subterranean to gracile gliding squirrels.
Membrane lipid adaptation of soil Gram-negative bacteria isolates to temperature and pH
Authors: Hellequin Eve , Collin Sylvie , Seder-Colomina Marina , Véquaud Pierre , Anquetil Christelle , Kish Adrienne , Huguet Arnaud 
Published: October 2022

Abstract3-hydroxy fatty acids (3-OH FAs) are characteristic components of the Gram-negative bacterial membrane, recently proposed as promising temperature and pH (paleo) proxies in soil. Nevertheless, to date, the relationships between the 3-OH FA distribution and temperature/pH are only based on empirical studies, with no work at the microbial level. This work investigated the influence of growth temperature and pH on the lipid profile in three strains of soil Gram-negative bacteria belonging to theBacteroidetesphylum. Even though the non-hydroxy FAs were more abundant than the 3-OH FAs in the investigated strains, we showed the important role of the 3-OH FAs in the membrane adaptation of Gram-negative bacteria to temperature. The strains shared a common adaptation mechanism to temperature, with a significant increase in the ratio ofanteisovs.isoornormal3-OH FAs at lower temperature. In contrast with temperature, no common adaptation mechanism to pH was noticed, the variations in the FA lipid profiles differing from one strain to another. The models envisioning the reconstruction of environmental changes in soils should include the whole suite of 3-OH FAs present in the membrane of Gram-negative bacteria, as all of them can be influenced by temperature or pH at the microbial level.