bluuebunny/crossref_metadata_2025_split huggingface dataset:
The comorbidity of HIV, hypertension and diabetes: a qualitative study exploring the challenges faced by healthcare providers and patients in selected urban and rural health facilities where the ICDM model is implemented in South Africa
Authors: Godongwana Motlatso , De Wet-Billings Nicole , Milovanovic Minja 
Published: July 2021

Abstract
Background
PLWH are living longer as a result of advancement and adherence to antiretroviral therapy. As the life expectancy of PLWH increases, they are at increased risk of hypertension and diabetes. HIV chronic co-morbidities pose a serious public health concern as they are linked to increased use and need of health services, decreased overall quality of life and increased mortality. While research shows that integrated care approaches applied within primary care settings can significantly reduce hospital admissions and mortality levels among patients with comorbidities, the primary care system in South Africa continues to be challenged with issues about the delivery of quality care.

Methods
This study applied a phenomenological qualitative research design. IDIs were conducted with 24 HCPs and adults living with the comorbidity of HIV and either hypertension or diabetes across two provinces in South Africa. The objective of the research was to understand the challenges faced by HCPs and patients in health facilities where the ICDM model is implemented. The health facilities were purposively sampled. However, the HCPs were recruited through snowballing and the patients through reviewing the facilities’ clinic records for participants who met the study criteria. All participants provided informed consent. The data was collected between March and May 2020. The findings were analysed inductively using thematic content analysis.

Results
The challenges experienced included lack of staff capacity, unclear guidelines on the delivery of integrated care for patients with HIV chronic comorbidities, pill burden, non-disclosure, financial burden, poor knowledge of treatments, relocation of patients and access to treatment. Lack of support and integrated chronic programmes including minimal information regarding the management of HIV chronic comorbidities were other concerns.

Conclusion
The outcomes of the ICDM model need to be strengthened and scaled up to meet the unique health needs and challenges of people living with HIV and other chronic conditions. Strengthening these outcomes includes providing capacity building and training on the delivery of chronic care treatment under the ICDM model, assisted self-management to improve patient responsibility of chronic disease management and strengthening activities for comorbidity health promotion.
Ultra-rare renal diseases diagnosed with whole-exome sequencing: Utility in diagnosis and management
Authors: Jung Jiwon , Lee Joo Hoon , Park Young Seo , Seo Go Hun , Keum Changwon , Kang Hee Gyung , Lee Hajeong , Lee Sang Koo , Lee Sang Taek , Cho Heeyeon , Lee Beom Hee 
Published: July 2021

AbstractBackgroundThis study aimed to use whole-exome sequencing (WES) to diagnose ultra-rare renal diseases and the clinical impact of such an approach on patient care.MethodsClinical, radiological, pathological, and genetic findings were reviewed in the patients and their family members.ResultsNine patients from nine unrelated Korean families were included in the study and evaluated. WES identified eight different conditions in these patients, i.e., autosomal dominant tubulointerstitial kidney disease associated withUMODmutation; recurrent urinary stones associated withAPRTdeficiency; Ayme-Gripp syndrome associated withMAFmutation; short rib-thoracic dysplasia associated withIFT140mutation; renal coloboma syndrome associated withPAX2mutations; idiopathic infantile hypercalcemia associated withCYP24A1mutation; and hypomagnesemia associated withTRPMmutation. Eleven different mutations, including seven novel mutations, were identified, i.e., four truncating mutations, six missense mutations, and one splice-acceptor variant. After genetic confirmation, strategies for the management of the following: medications, donor selection for renal transplantation, and surveillance for extra-renal manifestations were altered. In addition, genetic counseling was provided for the patients and their family members with respect to family member screening for affected but yet unidentified patients and future reproductive planning.ConclusionAs WES can effectively identify ultra-rare genetic renal diseases, facilitate the diagnosis process, and improve patient care, it is a good approach to enable a better understanding of ultra-rare conditions and for the establishment of appropriate counseling, surveillance, and management strategies.
Correction of complex three-dimensional deformities at the proximal femur using indirect reduction with angle blade plate and patient-specific instruments: a technical note
Authors: Jud Lukas , Vlachopoulos Lazaros , Grob Karl 
Published: July 2021

Abstract
Background
Corrective osteotomies for complex proximal femoral deformities can be challenging; wherefore, subsidies in preoperative planning and during surgical procedures are considered helpful. Three-dimensional (3D) planning and patient-specific instruments (PSI) are already established in different orthopedic procedures. This study gives an overview on this technique at the proximal femur and proposes a new indirect reduction technique using an angle blade plate.

Methods
Using computed tomography (CT) data, 3D models are generated serving for the preoperative 3D planning. Different guides are used for registration of the planning to the intraoperative situation and to perform the desired osteotomies with the following reduction task. A new valuable tool to perform the correction is the use of a combined osteotomy and implant-positioning guide, with indirect deformity reduction over an angle blade plate.

Results
An overview of the advantages of 3D planning and the use of PSI in complex corrective osteotomies at the proximal femur is provided. Furthermore, a new technique with indirect deformity reduction over an angle blade plate is introduced.

Conclusion
Using 3D planning and PSI for complex corrective osteotomies at the proximal femur can be a useful tool in understanding the individual deformity and performing the aimed deformity reduction. The indirect reduction over the implant is a simple and valuable tool in achieving the desired correction, and concurrently, surgical exposure can be limited to a subvastus approach.
Ketogenic diet for mitochondrial disease: a systematic review on efficacy and safety
Authors: Zweers Heidi , van Wegberg Annemiek M. J. , Janssen Mirian C. H. , Wortmann Saskia B. 
Published: July 2021

Abstract
Background
No curative therapy for mitochondrial disease (MD) exists, prioritizing supportive treatment for symptom relief. In animal and cell models ketones decrease oxidative stress, increase antioxidants and scavenge free radicals, putting ketogenic diets (KDs) on the list of management options for MD. Furthermore, KDs are well-known, safe and effective treatments for epilepsy, a frequent symptom of MD. This systematic review evaluates efficacy and safety of KD for MD.

Methods
We searched Pubmed, Cochrane, Embase and Cinahl (November 2020) with search terms linked to MD and KD. From the identified records, we excluded studies on Pyruvate Dehydrogenase Complex deficiency. From these eligible reports, cases without a genetically confirmed diagnosis and cases without sufficient data on KD and clinical course were excluded. The remaining studies were included in the qualitative analysis.

Results
Only 20 cases (14 pediatric) from the 694 papers identified met the inclusion criteria (one controlled trial (n = 5), 15 case reports). KD led to seizure control in 7 out of 8 cases and improved muscular symptoms in 3 of 10 individuals. In 4 of 20 cases KD reversed the clinical phenotype (e.g. cardiomyopathy, movement disorder). In 5 adults with mitochondrial DNA deletion(s) related myopathy rhabdomyolysis led to cessation of KD. Three individuals with POLG mutations died while being on KD, however, their survival was not different compared to individuals with POLG mutations without KD.

Conclusion
Data on efficacy and safety of KD for MD is too scarce for general recommendations. KD should be considered in individuals with MD and therapy refractory epilepsy, while KD is contraindicated in mitochondrial DNA deletion(s) related myopathy. When considering KD for MD the high rate of adverse effects should be taken into account, but also spectacular improvements in individual cases. KD is a highly individual management option in this fragile patient group and requires an experienced team. To increase knowledge on this—individually—promising management option more (prospective) studies using adequate outcome measures are crucial.
0.9% Sodium chloride solution versus Plasma-Lyte 148 versus compound sodium lacTate solution in children admitted to PICU—a randomized controlled trial (SPLYT-P): study protocol for an intravenous fluid therapy trial
Authors: Raman Sainath , Schibler Andreas , Marsney Renate Le , Trnka Peter , Kennedy Melanie , Mattke Adrian , Gibbons Kristen , Schlapbach Luregn J. 
Published: July 2021

Abstract
Background
Intravenous fluid therapy represents the most common intervention critically ill patients are exposed to. Hyperchloremia and metabolic acidosis associated with 0.9% sodium chloride have been observed to lead to worse outcomes, including mortality. Balanced solutions, such as Plasma-Lyte 148 and Compound Sodium Lactate, represent potential alternatives but the evidence on optimal fluid choices in critically ill children remains scarce. This study aims to demonstrate whether balanced solutions, when used as intravenous fluid therapy, are able to reduce the incidence of a rise in serum chloride level compared to 0.9% sodium chloride in critically ill children.

Methods
This is a single-centre, open-label randomized controlled trial with parallel 1:1:1 assignment into three groups: 0.9% sodium chloride, Plasma-Lyte 148, and Compound Sodium Lactate solutions for intravenous fluid therapy. The intervention includes both maintenance and bolus fluid therapy. Children aged < 16 years admitted to intensive care and receiving intravenous fluid therapy during the first 4 h of admission are eligible. The primary outcome measure is a ≥ 5mmol/L increase in serum chloride level within 48 h post-randomization. The enrolment target is 480 patients. The main analyses will be intention-to-treat.

Discussion
This study tests three types of intravenous fluid therapy in order to compare the risk of hyperchloremia associated with normal saline versus balanced solutions. This pragmatic study is thereby assessing the most common intervention in paediatric critical care.
This is a single-centre open-label study with no blinding at the level of delivery of the intervention. Certain paediatric intensive care unit (PICU) patient groups such as those admitted with a cardiac condition or following a traumatic brain injury are excluded from this study.

Trial registration
The study has received ethical approval (HREC/19/QCHQ/53177: 06/06/2019). It is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12619001244190) from 9th September 2019. Recruitment commenced on 12th November 2019. The primary results manuscript will be published in a peer-reviewed journal.
A study of the composition of the Obsoletus complex and genetic diversity of Culicoides obsoletus populations in Spain
Authors: Aguilar-Vega Cecilia , Rivera Belén , Lucientes Javier , Gutiérrez-Boada Isabel , Sánchez-Vizcaíno José Manuel 
Published: July 2021

Abstract
Background
The Culicoides obsoletus species complex (henceforth ‘Obsoletus complex’) is implicated in the transmission of several arboviruses that can cause severe disease in livestock, such as bluetongue, African horse sickness, epizootic hemorrhagic disease and Schmallenberg disease. Thus, this study aimed to increase our knowledge of the composition and genetic diversity of the Obsoletus complex by partial sequencing of the cytochrome c oxidase I (cox1) gene in poorly studied areas of Spain.

Methods
A study of C. obsoletus populations was carried out using a single-tube multiplex polymerase chain reaction (PCR) assay that was designed to differentiate the Obsoletus complex sibling species Culicoides obsoletus and Culicoides scoticus, based on the partial amplification of the cox1 gene, as well as cox1 georeferenced sequences from Spain available at GenBank. We sampled 117 insects of the Obsoletus complex from six locations and used a total of 238 sequences of C. obsoletus (ss) individuals (sampled here, and from GenBank) from 14 sites in mainland Spain, the Balearic Islands and the Canary Islands for genetic diversity and phylogenetic analyses.

Results
We identified 90 C. obsoletus (ss), 19 Culicoides scoticus and five Culicoides montanus midges from the six collection sites sampled, and found that the genetic diversity of C. obsoletus (ss) were higher in mainland Spain than in the Canary Islands. The multiplex PCR had limitations in terms of specificity, and no cryptic species within the Obsoletus complex were identified.

Conclusions
Within the Obsoletus complex, C. obsoletus (ss) was the predominant species in the analyzed sites of mainland Spain. Information about the species composition of the Obsoletus complex could be of relevance for future epidemiological studies when specific aspects of the vector competence and capacity of each species have been identified. Our results indicate that the intraspecific divergence is higher in C. obsoletus (ss) northern populations, and demonstrate the isolation of C. obsoletus (ss) populations of the Canary Islands.

Graphical abstract
Hematologic safety of 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer
Authors: Groener Daniel , Nguyen Cam Tu , Baumgarten Justus , Bockisch Benjamin , Davis Karen , Happel Christian , Mader Nicolai , Nguyen Ngoc Christina , Wichert Jennifer , Banek Severine , Mandel Philipp , Chun Felix K. H. , Tselis Nikolaos , Grünwald Frank , Sabet Amir 
Published: July 2021

Abstract
Background
Myelosuppression is a potential dose-limiting factor in radioligand therapy (RLT). This study aims to investigate occurrence, severity and reversibility of hematotoxic adverse events in patients undergoing RLT with 177Lu-PSMA-617 for metastatic castration-resistant prostate cancer (mCRPC). The contribution of pretreatment risk factors and cumulative treatment activity is taken into account specifically.

Methods
RLT was performed in 140 patients receiving a total of 497 cycles. A mean activity of 6.9 $$\pm$$
±
1.3 GBq 177Lu-PSMA-617 per cycle was administered, and mean cumulative activity was 24.6 $$\pm$$
±
15.9 GBq. Hematological parameters were measured at baseline, prior to each treatment course, 2 to 4 weeks thereafter and throughout follow-up. Toxicity was graded based on Common Terminology Criteria for Adverse Events v5.0.

Results
Significant (grade ≥ 3) hematologic adverse events occurred in 13 (9.3%) patients, with anemia in 10 (7.1%), leukopenia in 5 (3.6%) and thrombocytopenia in 6 (4.3%). Hematotoxicity was reversible to grade ≤ 2 through a median follow-up of 8 (IQR 9) months in all but two patients who died from disease progression within less than 3 months after RLT. Myelosuppression was significantly more frequent in patients with pre-existing grade 2 cytopenia (OR: 3.50, 95%CI 1.08–11.32, p = 0.04) or high bone tumor burden (disseminated or diffuse based on PROMISE miTNM, OR: 5.08, 95%CI 1.08–23.86, p = 0.04). Previous taxane-based chemotherapy was associated with an increased incidence of significant hematotoxicity (OR: 4.62, 95%CI 1.23–17.28, p = 0.02), while treatment with 223Ra-dichloride, cumulative RLT treatment activity and activity per cycle were not significantly correlated (p = 0.93, 0.33, 0.29).

Conclusion
Hematologic adverse events after RLT have an acceptable overall incidence and are frequently reversible. High bone tumor burden, previous taxane-based chemotherapy and pretreatment grade 2 cytopenia may be considered as risk factors for developing clinically relevant myelosuppression, whereas cumulative RLT activity and previous 223Ra-dichloride treatment show no significant contribution to incidence rates.
Time-delay effect on a diffusive predator–prey model with habitat complexity
Authors: Li Yanfeng , Liu Haicheng , Yang Ruizhi 
Published: July 2021

AbstractBased on the predator–prey system with a Holling type functional response function, a diffusive predator–prey system with digest delay and habitat complexity is proposed. Firstly, the stability of the equilibrium of diffusion system without delay is studied. Secondly, under the Neumann boundary conditions, taking time delay as the bifurcation parameter, by analyzing the eigenvalues of linearized operator of the system and using the normal form theory and center manifold method of partial functional differential equations, the effect of time delay on the stability of the system is studied and the conditions under which Hopf bifurcation occurs are given. In addition, the calculation formulas of the bifurcation direction and the stability of bifurcating periodic solutions are derived. Finally, the accuracy of theoretical analysis results is verified by numerical simulations and the biological explanation is given for the analysis results.
Clinicopathological characteristics of patients with paraproteinemia and renal damage
Authors: Tang Xuanli , Wan Feng , Yu Jin , Li Xiaohong , Yang Ruchun , Zhu Bin 
Published: July 2021

Abstract
Background
This study aimed to analyze the clinicopathological characteristics of patients with paraproteinemia and renal damage.

Methods
Ninety-six patients from 2014 to 2018 with paraproteinemia and renal damage were enrolled and the clinical data, renal pathology, treatment and prognosis data were collected.

Results
A total of 96 patients (54 male and 42 female), accounting for 2.7% of all renal biopsies, were enrolled in this study. Among them, 42 were monoclonal gammopathy of renal significance (MGRS), 21 were renal monotypic immunoglobulin alone (renal monoIg), and 19 were monoclonal gammopathy of undetermined significance (MGUS). Individuals with multiple myeloma (MM) accounted for the fewest number of patients (n  =  14). In the MGRS group, the main diseases were amyloidosis (n  =  25) and cryoglobulinemic glomerulonephritis (n  =  7), while in the MM group, the main diseases were cast nephropathy (n  =  9) and light chain deposit disease (n  =  3). In the MGUS group, it was mainly IgA nephropathy (IgAN, n  =  10) and idiopathic membranous nephropathy (n  =  5); while in the renal monoIg group, most of the cases were IgAN (n  =  19). Chemotherapy was mainly administered to patients in the MM group, while immunosuppression therapy was mostly administered to patients in the renal monoIg group. Most patients with renal monoIg exhibited a major response, followed by the patients with MGUS and MGRS, while most of the patients with MM had a partial response but none had a major response. Approximately more than half (57.1%) of the patients with MM progressed to end-stage renal disease (ESRD), followed by MGRS (33.3%); however, the mortality rate was low in both the MGRS and MM groups. The survival analysis reviewed that serum creatinine, hemoglobin levels, and the serum κ/λ ratio were independent risk factors for ESRD in patients with MGRS.

Conclusions
The clinicopathological changes in patients with MGRS were between those in patients with MM and MGUS. The treatment for MGRS and MM was more intensive, and the overall mortality rate was low. Both MGUS and renal monoIg alone exhibited slighter clinicopathological features than MGRS and MM, and the treatment was focused mostly on primary renal diseases.
Temporal patterns in Ixodes ricinus microbial communities: an insight into tick-borne microbe interactions
Authors: Lejal E. , Chiquet J. , Aubert J. , Robin S. , Estrada-Peña A. , Rue O. , Midoux C. , Mariadassou M. , Bailly X. , Cougoul A. , Gasqui P. , Cosson J. F. , Chalvet-Monfray K. , Vayssier-Taussat M. , Pollet T. 
Published: July 2021

AbstractBackgroundTicks transmit pathogens of medical and veterinary importance and are an increasing threat to human and animal health. Assessing disease risk and developing new control strategies requires identifying members of the tick-borne microbiota as well as their temporal dynamics and interactions.MethodsUsing high-throughput sequencing, we studied theIxodes ricinus microbiota and its temporal dynamics. 371 nymphs were monthly collected during three consecutive years in a peri-urban forest. After a Poisson lognormal model was adjusted to our data set, a principal component analysis, sparse network reconstruction, and differential analysis allowed us to assess seasonal and monthly variability ofI. ricinusmicrobiota and interactions within this community.ResultsAround 75% of the detected sequences belonged to five genera known to be maternally inherited bacteria in arthropods and to potentially circulate in ticks:CandidatusMidichloria,Rickettsia,Spiroplasma,ArsenophonusandWolbachia. The structure of theI. ricinusmicrobiota varied over time with interannual recurrence and seemed to be mainly driven by OTUs commonly found in the environment. Total network analysis revealed a majority of positive partial correlations. We identified strong relationships between OTUs belonging toWolbachiaandArsenophonus, evidence for the presence of the parasitoid waspIxodiphagus hookeriin ticks. Other associations were observed between the tick symbiontCandidatusMidichloria and pathogens belonging toRickettsia. Finally, more specific network analyses were performed on TBP-infected samples and suggested that the presence of pathogens belonging to the generaBorrelia,AnaplasmaandRickettsiamay disrupt microbial interactions inI. ricinus.ConclusionsWe identified theI. ricinusmicrobiota and documented marked shifts in tick microbiota dynamics over time. Statistically, we showed strong relationships between the presence of specific pathogens and the structure of theI. ricinusmicrobiota. We detected close links between some tick symbionts and the potential presence of either pathogenicRickettsiaor a parasitoid in ticks. These new findings pave the way for the development of new strategies for the control of ticks and tick-borne diseases.