bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comprehensive genotype–phenotype evaluation of eight Chinese probands with Waardenburg syndrome
Authors: Li Sijun , Qin Mengyao , Mao Shuang , Mei Lingyun , Cai Xinzhang , Feng Yong , He Chufeng , Song Jian 
Published: November 2022

Abstract
Background
Waardenburg syndrome (WS) is the most common form of syndromic deafness with phenotypic and genetic heterogeneity in the Chinese population. This study aimed to clarify the clinical characteristics and the genetic cause in eight Chinese WS families (including three familial and five sporadic cases). Further genotype–phenotype relationships were also investigated.

Methods
All probands underwent screening for the known WS-related genes including PAX3, SOX10, MITF, EDNRB, EDN3, and SNAI2 using next-generation sequencing to identify disease-causing genes. Further validation using Sanger sequencing was performed. Relevant findings for the associated genotype–phenotype from previous literature were retrospectively analyzed.

Result
Disease-causing variants were detected in all eight probands by molecular genetic analysis of the WS genes (SOX10(NM_006941.4): c.544_557del, c.553 C > T, c.762delA, c.336G > A; MITF(NM_000248.3): c.626 A > T; PAX3(NM_181459.4): c.838delG, c.452-2 A > G, c.214 A > G). Six mutations (SOX10:c.553 C > T, c.544_557del, c.762delA; PAX3: c.838delG, c.214 A > G; MITF:c.626 A > T) were first reported. Clinical evaluation revealed prominent phenotypic variability in these WS patients. Twelve WS1 cases and five WS2 cases were diagnosed in total. Two probands with SOX10 mutations developed progressive changes in iris color with age, returning from pale blue at birth to normal tan. Additionally, one proband had a renal malformation (horseshoe kidneys).All cases were first described as WS cases. Congenital inner ear malformations were more common, and semicircular malformations were exclusively observed in probands with SOX10 mutations. Unilateral hearing loss occurred more often in cases with PAX3 mutations.

Conclusion
Our findings helped illuminate the phenotypic and genotypic spectrum of WS in Chinese populations and could contribute to better genetic counseling of WS.
Malaria diagnostic and treatment practices for febrile children under 5 years at two general hospitals in Karamoja, a high transmission setting in Uganda
Authors: Zalwango Jane Frances , Nankabirwa Joaniter I. , Kitutu Freddy Eric , Akunzirwe Rebecca , Buhuguru Remmy , Rokani Joan Bayowa , Ssendikwanawa Emmanuel , Kiguli Sarah , Arinaitwe Emmanuel , Kalyango Joan N. 
Published: November 2022

Abstract
Background
Malaria is one of the leading causes of morbidity and mortality among children under 5 years of age in Uganda. Although Karamoja sub-region has the highest prevalence of malaria, and one of the highest case fatality rates in children under 5 years, information on malaria case management for the sub-region is scarce. The study evaluated the malaria diagnostic and treatment practices, as well as the factors associated with inappropriate care for children under 5 years of age presenting with fever in two public hospitals within the sub-region.

Methods
A cross-sectional study was conducted amongst 857 children under 5 years of age who presented with fever at Abim and Kaabong general hospitals between February and March 2020. A questionnaire was administered to the primary caregiver during exit/bedside interviews to collect socio-demographic information. The participant clinical notes were reviewed to capture information on laboratory tests conducted, diagnosis given, and treatment prescribed. In addition, a health facility assessment was conducted and information on healthcare workers was collected. The healthcare worker and facility data was linked to the participant’s hospital visit. Main outcome measures were malaria diagnostic and treatment practices.

Results
Of the 857 children enrolled, 820 (95.7%) had a malaria diagnostic test done and 623 (76.0%) tested positive for malaria. All test positive children received anti-malarial treatment, however, only 424/623 (68.1%) received the recommended anti-malarial drug and 376/424 (88.7%) received the right dose of the treatment. Inappropriate diagnosis/treatment was in 321 (37.5%) of the enrolled participants. Factors associated with inappropriate diagnosis/treatment included: lack of recommended anti-malarials on the day of the visit (Prevalence Ratio [PR] = 2.1, 95% confidence interval [CI] 1.8–2.4), hospital where care was sought (PR = 0.4, 95% CI 0.3–0.5), being managed by a recently supervised health worker (PR = 0.5, 95% CI 0.2–0.9), and health worker cadre (PR = 0.8, 95% CI 0.7–0.9).

Conclusion
The prevalence of inappropriate malaria diagnosis and treatment in the Karamoja sub-region was high with approximately one in every three children receiving inappropriate care. This was majorly influenced by health system factors, which if improved upon may reduce malaria-related mortalities in the sub-region a vital step in meeting the country’s target of zero deaths from malaria by 2030.
Antibiofilm activity of ultra-small gold nanoclusters against Fusobacterium nucleatum in dental plaque biofilms
Authors: Zhang Yangheng , Chen Rixin , Wang Yuxian , Wang Peng , Pu Jiajie , Xu Xiaoqiang , Chen Faming , Jiang Ling , Jiang Qing , Yan Fuhua 
Published: November 2022

AbstractPathogenic dental plaque biofilms are universal and harmful, which can result in oral infections and systemic diseases. Many conventional therapeutic methods have proven insufficient or ineffective against plaque biofilms. Therefore, new strategies are urgently needed. Fusobacterium nucleatum (F. nucleatum), a periodontal pathogen associated with a variety of oral and systemic diseases, is thought to be central to the development and structure of dental plaques. Here, ultra-small gold nanoclusters (AuNCs) were prepared. They exhibited potent antibacterial activity against F. nucleatum through enhanced destruction of bacterial membranes and generation of reactive oxygen species. Furthermore, due to their excellent penetration, the AuNCs could inhibit biofilm formation and destroy mature biofilms in vitro. Their antibiofilm efficacy was further confirmed in a mouse model, where they reduced biofilm accumulation and ameliorated inflammation. Meanwhile, the disruption of oral and gut microbiota caused by colonization of oral F. nucleatum could be partially restored through AuNCs treatment. Therefore, AuNCs could be considered as promising antibiofilm agents and have great potential in the clinical treatment of dental plaque.
Graphical Abstract
Taking the cat-and-mouse game to the next level: different perspectives on the introduction of the German New Psychoactive Substances Act
Authors: Kühnl Regina , Aydin Darya , Horn Sabine , Olderbak Sally , Verthein Uwe , Kraus Ludwig 
Published: November 2022

Abstract
Background
To counteract the spread of new psychoactive substances (NPS) and to prevent the emergence of novel substances, specifically designed as a response to the legal control of individual substances, a new law was introduced in Germany in 2016: the New Psychoactive Substances Act (NpSG). The NpSG combines a generic approach with the waiver of criminal liability for the acquisition and possession of NPS for personal use, which is a novelty in German narcotics law. The present study aimed at exploring the impact of the introduction of the NpSG from three different perspectives—NPS users, staff of addiction care facilities, and members of law enforcement authorities—to better understand the dynamics surrounding such a change in legislation and to contribute to the body of international experience in dealing with NPS.

Methods
Semi-structured narrative interviews were conducted with a total of 193 representatives of the three different groups affected by the law. These interviews included questions on perceived changes associated with the introduction of the NpSG as well as questions on opinions regarding legal and criminal policy issues. The analysis was carried out using qualitative content analysis according to Mayring.

Results
Most interviewees welcomed the non-criminalisation approach of the NpSG but also noticed that, in practice, not much has changed for users. Nevertheless, the changes in legislation have had an impact on the market. For example, novel substances have emerged circumventing the new legislation. According to users, this has led some to reduce NPS use and others to adopt more hazardous consumption patterns. Overall, most respondents did not expect the introduction of the NpSG to bring any significant changes.

Conclusions
Although the idea of non-criminalisation inherent to the NpSG is appreciated and the generic approach has been well implemented in the law, thus covering a wide range of substances, the introduction of the law—perhaps for that very reason—has also had unintended and negative consequences, taking the cat-and-mouse game to the next level. To end the game, or at least to defuse the game situation, a combination of different strategies will be necessary, with legislation always playing a key role.
Tripartite motif-containing protein 46 accelerates influenza A H7N9 virus infection by promoting K48-linked ubiquitination of TBK1
Authors: Su Wei , Lin Xian-Tian , Zhao Shuai , Zheng Xiao-Qin , Zhou Yu-Qing , Xiao Lan-Lan , Chen Hui , Zhang Zheng-Yu , Zhang Li-Jun , Wu Xiao-Xin 
Published: November 2022

Abstract
Background
Avian influenza A H7N9 emerged in 2013, threatening public health and causing acute respiratory distress syndrome, and even death, in the human population. However, the underlying mechanism by which H7N9 virus causes human infection remains elusive.

Methods
Herein, we infected A549 cells with H7N9 virus for different times and assessed tripartite motif-containing protein 46 (TRIM46) expression. To determine the role of TRIM46 in H7N9 infection, we applied lentivirus-based TRIM46 short hairpin RNA sequences and overexpression plasmids to explore virus replication, and changes in type I interferons and interferon regulatory factor 3 (IRF3) phosphorylation levels in response to silencing and overexpression of TRIM46. Finally, we used Co-immunoprecipitation and ubiquitination assays to examine the mechanism by which TRIM46 mediated the activity of TANK-binding kinase 1 (TBK1).

Results
Type I interferons play an important role in defending virus infection. Here, we found that TRIM46 levels were significantly increased during H7N9 virus infection. Furthermore, TRIM46 knockdown inhibited H7N9 virus replication compared to that in the control group, while the production of type I interferons increased. Meanwhile, overexpression of TRIM46 promoted H7N9 virus replication and decrease the production of type I interferons. In addition, the level of phosphorylated IRF3, an important interferon regulatory factor, was increased in TRIM46-silenced cells, but decreased in TRIM46 overexpressing cells. Mechanistically, we observed that TRIM46 could interact with TBK1 to induce its K48-linked ubiquitination, which promoted H7N9 virus infection.

Conclusion
Our results suggest that TRIM46 negatively regulates the human innate immune response against H7N9 virus infection.
An observational study to investigate the relationship between plasma glucosylsphingosine (lyso-Gb1) concentration and treatment outcomes of patients with Gaucher disease in Japan
Authors: Ida Hiroyuki , Watanabe Yuko , Sagara Rieko , Inoue Yoichi , Fernandez Jovelle 
Published: November 2022

Abstract
Background
Gaucher disease (GD) is an autosomal recessive disease caused by GBA1 mutations resulting in glucosylceramide accumulation in macrophages. GD is characterized by hepatosplenomegaly, anemia, thrombocytopenia, bone complications, and neurological complications. Glucosylsphingosine (lyso-Gb1), a deacylated form of glucosylceramide, has been identified as a promising biomarker for the diagnosis and treatment response in GD. The aim of this study was to examine the relationship between plasma lyso-Gb1 and therapeutic goals for GD (improvements in hepatomegaly, splenomegaly, anemia, thrombocytopenia, bone pain, and bone crisis), as well as disease type and GBA1 mutation type, in Japanese patients with GD receiving velaglucerase alfa, an enzyme replacement therapy (ERT). Furthermore, this study compared the plasma lyso-Gb1 concentration observed in Japanese patients included in this study with that observed in a previous non-Japanese clinical study.

Results
This non-interventional, open-label, multicenter observational cohort study (October 2020 to March 2021) included a total of 20 patients (of any age) with GD (type 1: n = 8; type 2: n = 9; type 3: n = 3) treated with velaglucerase alfa for ≥ 3 months. Median (minimum–maximum) duration of velaglucerase alfa treatment was 49.5 (3–107) months. A total of 14 (70.0%) patients achieved all therapeutic goals (i.e., 100% achievement; improvements in hepatomegaly, splenomegaly, anemia, thrombocytopenia, bone pain, and bone crisis). Overall, median (minimum–maximum) lyso-Gb1 concentration was 24.3 (2.1–150) ng/mL. Although not statistically significant, numerically lower plasma lyso-Gb1 concentrations were observed in patients with 100% achievement compared with those without; no statistically significant difference in plasma lyso-Gb1 concentration was observed between patients with different disease type or mutation type. Furthermore, lyso-Gb1 concentrations observed in Japanese patients were numerically lower than that observed in a previous study of non-Japanese patients with GD receiving ERT.

Conclusions
In this study, high achievement rates of therapeutic goals with low lyso-Gb1 concentration were observed, demonstrating a correlation between therapeutic goals and lower plasma lyso-Gb1 concentration in Japanese patients with GD treated with velaglucerase alfa. This study further suggests that plasma lyso-Gb1 concentration may be a useful biomarker for treatment response in patients with GD.
QSRR modeling of the chromatographic retention behavior of some quinolone and sulfonamide antibacterial agents using firefly algorithm coupled to support vector machine
Authors: Fouad Marwa A. , Serag Ahmed , Tolba Enas H. , El-Shal Manal A. , El Kerdawy Ahmed M. 
Published: November 2022

AbstractQuinolone and sulfonamide are two classes of antibacterial agents with an opulent history of medicinal chemistry features that contribute to their bacterial spectrum, efficacy, pharmacokinetics, and adverse effect profiles. The urgent need for their use, combined with the escalating rate of their resistance, necessitates the development of suitable analytical methods that accelerate and facilitate their analysis. In this study, the advanced firefly algorithm (FFA) coupled with support vector regression (SVR) was used to select the most significant descriptors and to construct two quantitative structure-retention relationship (QSRR) models using a series of 11 selected quinolone and 13 sulfonamide drugs, respectively, to predict their retention behavior in HPLC. Precisely, the effect of the pH value and acetonitrile composition in the mobile phase on the retention behavior of quinolones and sulfonamides, respectively, were studied. The obtained QSRR models performed well in both internal and external validations, demonstrating their robustness and predictive ability. Y-randomization validation demonstrated that the obtained models did not result by statistical chance. Moreover, the obtained results shed the light on the molecular features that influence the retention behavior of these two classes under the current chromatographic conditions.
Sequencing of hsp70 for discernment of species from the Leishmania (Viannia) guyanensis complex from endemic areas in Colombia
Authors: Hoyos Juliana , Rosales-Chilama Mariana , León Cielo , González Camila , Gómez María Adelaida 
Published: November 2022

Abstract
Background
Colombia is ranked very high among countries with the highest numbers of endemic Leishmania species (n = 9) causing human disease. Although much effort has been devoted to generating simple and specific tools for Leishmania species identification, challenges remain in the discrimination of species belonging to the Leishmania (Viannia) guyanensis complex: L. (V.) guyanensis and L. (V.) panamensis.

Methods
A set of seven reference strains of species belonging to the L. (Leishmania) and L. (Viannia) subgenera, clinical strains from human cases of cutaneous leishmaniasis (CL; n = 26) and samples collected from sylvatic mammals and sand flies (n = 7) from endemic areas in Colombia were analyzed in this study. The heat-shock protein 70 gene (hsp70) was amplified by PCR from DNA extracted from logarithmic-phase promastigotes or tissue samples, and the PCR products were sequenced. Sequence alignment was performed against a set of previously published and curated sequences, and phylogenetic analysis based on the maximum-likelihood and Bayesian inference approaches was conducted. Haplotype diversity among strains and species of the L. (V.) guyanensis complex was explored using a median-joining network.

Results
Sequencing of the hsp70 gene for L. (Viannia) spp. typing was comparable to species identification using isoenzyme electrophoresis or monoclonal antibodies. Complete species matching was found, except for one sylvatic sample with an identity yet unsolved. Among the L. (V.) panamensis clinical strains, two distinctive phylogenetic clusters were found to correlate with two different zymodemes: L. (V.) panamensis Z2.2 and Z2.3. Analysis of samples from sylvatic environments identified novel records of naturally infected wild mammal and sand fly species.

Conclusions
Our results support the adequacy of hsp70 gene sequencing as a single-locus approach for discrimination of L. (Viannia) spp., as well as for exploring the genetic diversity within the L. (V.) guyanensis complex.

Graphical Abstract
No association between habitat, autogeny and genetics in Moroccan Culex pipiens populations
Authors: Arich Soukaina , Haba Yuki , Assaid Najlaa , Fritz Megan L. , McBride Carolyn S. , Weill Mylène , Taki Hassan , Sarih M’hammed , Labbé Pierrick 
Published: November 2022

Abstract
Background
Mosquitoes of the Culex pipiens complex are found across the globe and are the focus of many research studies. Among the temperate species C. pipiens sensu stricto (s.s.), two forms are usually described: molestus and pipiens. These two forms are indistinguishable in terms of morphology but show behavioral and physiological differences that may have consequences for their associated epidemiology. The two forms are well defined in the northern part of the species distribution, where autogeny is strictly associated with the molestus form. However, whether the two remain distinct and show the characteristic differences in behavior is less clear in North Africa, at the southern edge of their range.

Methods
The association between autogeny, as determined by ovarian dissection, and molecular forms, based on the CQ11 microsatellite marker, was studied in six Moroccan populations of C. pipiens.

Results
An overall low prevalence of autogeny was found at three of the Moroccan regions studied, although it reached 17.5% in the Agadir population. The prevalence of form-specific CQ11 alleles was quite similar across all populations, with the molestus allele being rarer (approx. 15%), except in the Agadir population where it reached 43.3%. We found significant deficits in heterozygotes at the diagnostic CQ11 locus in three populations, but the three other populations showed no significant departure from panmixia, which is in line with the results of a retrospective analysis of the published data. More importantly, we found no association between the autogeny status and CQ11 genotypes, despite the many females analyzed.

Conclusions
There was limited evidence for two discrete forms in Morocco, where individuals carrying pipiens and molestus alleles breed and mate in the same sites and are equally likely to be capable of autogeny. These observations are discussed in the epidemiological context of Morocco, where C. pipiens is the main vector of several arboviruses.

Graphical Abstract
High prevalence of canine heartworm, Dirofilaria immitis, in pet dogs in south Texas, USA, with evidence of Aedes aegypti mosquitoes contributing to transmission
Authors: Scavo Nicole A. , Zecca Italo B. , Sobotyk Caroline , Saleh Meriam N. , Lane Sarah K. , Olson Mark F. , Hamer Sarah A. , Verocai Guilherme G. , Hamer Gabriel L. 
Published: November 2022

AbstractBackgroundThe canine heartwormDirofilaria immitis,a filarioid nematode of dogs and other carnivores, is widespread in the USA and the world. Over 20 different mosquito species serve as intermediate hosts ofD. immitis, but their contribution to transmission varies according to factors like host feeding patterns, geographic locations and climatic conditions. The yellow fever mosquito,Aedes aegypti,is a competent vector ofD. immitisbut is often dismissed as a vector of veterinary relevance given its anthropophilic feeding behavior. We evaluated the prevalence ofD.immitisin pet dogs along the USA-Mexico border and assessed whetherAe.aegyptiin the area are naturally infected with heartworm and are potentially acting as a vector.MethodsA total of 200 whole blood samples collected from pet dogs in the Lower Rio Grande Valley in south Texas from 2016 to 2019 were included in this study. Canine serum samples forD. immitiswere tested using the DiroCHEK® Canine Heartworm Antigen Test Kit pre- and post-immune complex dissociations (ICD) and blood samples were tested using high-resolution melt (HRM) quantitative PCR (qPCR) and a probe-based qPCR. Additionally, mosquito specimens were collected and identified, andAe. aegyptiheads, abdomens and pools were tested using conventional PCR (cPCR) and HRM qPCR.ResultsOverall, heartworm prevalence in dogs aged > 6 months was 40.8% (64/157) when the results from all testing modalities were considered. Heartworm antigen was detected in 33.5% and 40.7% of the dogs using DiroCHEK® pre- and post-ICD, respectively. By molecular screening, 20.1% of dogs tested positive with probe-based qPCR, while only one tested positive with HRM qPCR. Of theAe. aegyptiabdomens from blood-fedAe. aeygptitested, 20 (21.7%) from mosquitoes that fed on dogs and four (7%) from those that fed on humans tested positive for heartworm. AmongAe. aegyptiheads from blood-fedAe. aeygpti, two (1.1%) were positive based on cPCR and four (2.5%) were positive based on HRM qPCR. NoD. immitisDNA was detected in the 208 pools of whole bodies (358 individuals) ofAe. aegyptigravid females.ConclusionsOur study highlights a high prevalence of heartworm in dogs in south Texas and provides evidence thatAe. aegypticould be contributing to heartworm transmission in canine populations in this region.Graphical Abstract