bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical trials in-a-dish for cardiovascular medicine
Authors: Wu Xuekun , Swanson Kyle , Yildirim Zehra , Liu Wenqiang , Liao Ronglih , Wu Joseph C
Published: September 2024

Cardiovascular diseases persist as a global health challenge that requires methodological innovation for effective drug development. Conventional pipelines relying on animal models suffer from high failure rates due to significant interspecies variation between humans and animal models. In response, the recently enacted Food and Drug Administration Modernization Act 2.0 encourages alternative approaches including induced pluripotent stem cells (iPSCs). Human iPSCs provide a patient-specific, precise, and screenable platform for drug testing, paving the way for cardiovascular precision medicine. This review discusses milestones in iPSC differentiation and their applications from disease modelling to drug discovery in cardiovascular medicine. It then explores challenges and emerging opportunities for the implementation of ‘clinical trials in-a-dish’. Concluding, this review proposes a framework for future clinical trial design with strategic incorporations of iPSC technology, microphysiological systems, clinical pan-omics, and artificial intelligence to improve success rates and advance cardiovascular healthcare.
Dual-chamber vs. single-chamber pacemaker in patients in sinus rhythm with an atrioventricular block: a nationwide cohort study
Authors: Bodin Alexandre , Texier Ivann , Bisson Arnaud , Pierre Bertrand , Herbert Julien , Jacobs Mathieu , Nasarre Mathieu , Bernard Anne , Fauchier Laurent
Published: September 2024

Aims

In complete atrioventricular block (AVB) with underlying sinus rhythm, it is recommended to implant a dual-chamber pacemaker rather than a single-chamber pacemaker. However, no large-scale study has been able to demonstrate the superiority of this choice on hard clinical criteria such as morbimortality.

Methods and results

This retrospective observational study included all patients who received a primary pacemaker implantation in the indication of complete AVB with underlying sinus rhythm in France, based on the national administrative database between January 2013 and December 2022. After propensity score matching, we obtained two groups containing 19 219 patients each. The incidence of all-cause mortality was 9.22%/year for the dual-chamber pacemaker group, compared with 11.48%/year for the single-chamber pacemaker group (hazard ratio (HR) 0.807, P < 0.0001]. Similarly, there was a lower incidence of cardiovascular mortality (HR 0.766, P < 0.0001), heart failure (HR 0.908, P < 0.0001), atrial fibrillation (HR 0.778, P < 0.0001), and ischaemic stroke (HR 0.873, P = 0.008) in the dual-chamber pacemaker group than in the single-chamber pacemaker group. Regarding re-interventions and complications, there were fewer upgrades (addition of atrial lead or left ventricular lead) in the dual-chamber group (HR 0.210, P < 0.0001), but more haematomas (HR 1.179, P = 0.006) and lead repositioning (HR 1.123, P = 0.04).

Conclusion

In the indication of complete AVB with underlying sinus rhythm, our results are consistent with current recommendations to prefer implantation of a dual-chamber pacemaker rather than a single-chamber pacemaker for these patients. Implantation of a dual-chamber pacemaker is associated with a lower risk of mortality, heart failure, atrial fibrillation, and stroke during follow-up.
Causative genes of intrinsic hybrid incompatibility in animals and plants: what we have learned about speciation from the molecular perspective
Authors: Kitano Jun , Okude Genta
Published: September 2024

Intrinsic hybrid incompatibility is one of the important reproductive isolating barriers between species. Several genes causing intrinsic hybrid incompatibilities have been identified over the last few decades. Information on these causative genes and mutations of intrinsic hybrid incompatibilities helps us answer several important evolutionary questions regarding the plausibility of classic theoretical models of intrinsic hybrid incompatibilities, the evolutionary driving forces involved, and the repeatability of molecular mechanisms across taxa. Here, we provide an updated list of the causative genes of intrinsic hybrid incompatibilities in animals and plants. Although several empirical cases are consistent with the classic two-locus Dobzhansky–Muller incompatibility model, there are many cases in which epistatic interactions are more complex. Animals and plants appear to share several molecular mechanisms of intrinsic hybrid incompatibility. In both animals and plants, many causative genes evolve under genomic conflicts. Some taxonomic differences may result from inherent physiological differences. As most studies are biased toward a limited number of model organisms, further studies on natural systems across diverse taxa are necessary for the quantitative assessment of these patterns in nature.
A microbial perspective on speciation
Authors: Stelkens Rike
Published: September 2024

Understanding what a microbial species is and the process of speciation in microbes has been and still is a puzzle with many challenges. But there is now emerging consensus that speciation in microbes does follow certain rules and limitations. Just like in macrobes, it can be driven by divergent natural selection and is maintained by barriers to gene flow, either genetic or ecological in nature. However, whether microbial speciation mirrors that of sexually reproducing eukaryotes is up for debate, as extensive horizontal gene flow can blur patterns and processes. Here, I provide intriguing examples of speciation in bacteria, viruses, and yeast, which are arguably similar to what we see in eukaryotes. I synthesize recent insights from microbial evolutionary genomics, which may mitigate the traditional view that microbes are ‘messy’ and do not fit eukaryotic species concepts and speciation models. Finally, I highlight the benefits of microbial experimental evolution to answer fundamental questions in speciation research (especially why, how, and when speciation occurs). Speciation research with microbes, as opposed to the organisms traditionally used in this field, may suffer less from observational bias and the experimental control we have over selection types, gene flow, and reproductive modes in microbial systems may allow us to determine the mechanisms and timing of ecological divergence, reproductive isolation, and speciation.
A universal and constant rate of gene content change traces pangenome flux to LUCA
Authors: Trost Katharina , Knopp Michael R , Wimmer Jessica L E , Tria Fernando D K , Martin William F
Published: September 2024

Prokaryotic genomes constantly undergo gene flux via lateral gene transfer, generating a pangenome structure consisting of a conserved core genome surrounded by a more variable accessory genome shell. Over time, flux generates change in genome content. Here, we measure and compare the rate of genome flux for 5655 prokaryotic genomes as a function of amino acid sequence divergence in 36 universally distributed proteins of the informational core (IC). We find a clock of gene content change. The long-term average rate of gene content flux is remarkably constant across all higher prokaryotic taxa sampled, whereby the size of the accessory genome—the proportion of the genome harboring gene content difference for genome pairs—varies across taxa. The proportion of species-level accessory genes per genome, varies from 0% (Chlamydia) to 30%–33% (Alphaproteobacteria, Gammaproteobacteria, and Clostridia). A clock-like rate of gene content change across all prokaryotic taxa sampled suggest that pangenome structure is a general feature of prokaryotic genomes and that it has been in existence since the divergence of bacteria and archaea.
Stair Climbing, Genetic Predisposition, and the Risk of Hip/Knee Osteoarthritis
Authors: Wei Yingliang , Zhang Tingjing , Wang Haochen , Su Jianbang , Yu Minghao , Liu Yashu , Bai Lunhao , Xia Yang
Published: September 2024

Background

Few studies have explored the association between stair climbing and osteoarthritis (OA) to determine whether the former is a protective or risk factor for the latter. This study prospectively evaluated the associations among stair climbing, genetic susceptibility, and their interaction with the risk of incident hip/knee OA.

Methods

The cohort analyses included 398 939 participants from the UK Biobank. Stair climbing was assessed using a questionnaire. Genetic risk scores consisting of 70, 83, and 87 single-nucleotide polymorphisms for hip, knee, and hip/knee OA were constructed. Cox proportional hazard regression models were used to estimate hazard ratios and 95% confidence intervals for the associations among stair climbing, genetic predisposition, and hip and/or knee OA risk.

Results

After 3 621 735 person-years of follow-up, 31 940 patients developed OA. Stair climbing was positively associated with incident hip/knee (p for trend < .001) and knee (p for trend < .0001) OA but not hip OA. After adjustments, compared with no stair climbing, climbing >150 steps/d was associated with a higher risk of hip/knee OA (hazard ratio, 1.08; 95% confidence interval: 1.03–1.12) and knee OA (hazard ratio, 1.13; 95% confidence interval, 1.06–1.20). Although no significant interaction between stair climbing and the genetic risk scores of OA risk was found, the above associations were only significant in participants with middle and high genetic risk scores.

Conclusions

A higher frequency of stair climbing was positively associated with the risk of knee OA but not hip OA, highlighting the importance of avoiding frequent stair climbing in preventing knee OA, especially in genetically predisposed individuals.
Social Isolation and Hospitalization in Community-Dwelling Older Adults by Dementia Status
Authors: Pomeroy Mary Louise , Umoh Mfon , Qian Yiqing , Gimm Gilbert , Ornstein Katherine A , Cudjoe Thomas K M
Published: September 2024

Background

Social isolation is a well-known risk factor for poor health outcomes, including incident dementia, yet its associations with outcomes among persons living with dementia are understudied. We examined the association between social isolation and hospitalization among a nationally representative sample of older adults with and without dementia.

Methods

This observational cohort study included 5 533 community-dwelling Medicare beneficiaries from the 2015 and 2016 National Health and Aging Trends Study (NHATS). Using multivariable logistic regression analyses, we examined associations between social isolation and hospitalization in the following year, examining differences by dementia status. Social isolation was measured using a 4-item typology. Dementia was identified using a prespecified classification in NHATS.

Results

20.7% of older adults were socially isolated. Social isolation was more prevalent among persons with dementia (35.4%) than among those without dementia (19.0%) (p < .001). Among persons with dementia, social isolation was associated with 1.68 greater odds of hospitalization (confidence interval [CI]: 1.23–2.28), translating into a 9% average increase in the predicted probability of hospitalization for persons with dementia who were socially isolated compared to those who were not (p = .001). In the combined sample that included persons with and without dementia, there was a significant moderation effect of dementia on the association between social isolation and hospitalization (odds ratio: 1.70; CI: 1.19–2.43).

Conclusions

For persons with dementia, social isolation is prevalent and associated with greater odds of subsequent hospitalization. Efforts to reduce acute healthcare utilization should explore ways to bolster social connection to improve health outcomes among persons with dementia.
Worrying Across the Generations: The Impact of Adult Grandchildren’s Problems on Grandparents’ Well-Being
Authors: Frase Robert T , Suitor J Jill , Gilligan Megan , Stepniak Catherine , Ogle Destiny , Fingerman Karen L
Published: September 2024

Objectives

The intergenerational stake hypothesis and theories of the life course posit that older generations are invested in the well-being of younger generations. Consistent with this, previous research has shown that adult children’s problems are associated with worse parental well-being. Because multigenerational ties have become increasingly important in the 21st century, we propose that adult grandchildren’s problems may also impact grandparents’ well-being. In this paper, we test this hypothesis and investigate the moderating effects of grandparents’ race and maternal/paternal status.

Methods

The analytic sample includes 206 grandparents aged 65–95 who participated in the second wave of the Family Exchanges Study. Adult grandchildren’s problems were operationalized as the proportions of adult grandchildren who experienced (1) physical–emotional problems and (2) lifestyle–behavioral problems.

Results

Main effects multilevel analyses suggested that adult grandchildren’s problems did not predict grandparents’ well-being. However, moderation analyses revealed that the association between grandparents’ depressive symptoms and adult grandchildren’s physical–emotional problems was larger among Black than White grandparents, and maternal than paternal grandparents. Adult grandchildren’s lifestyle–behavioral problems did not predict grandparents’ depression, and these effects were not conditioned by race or maternal/paternal status.

Discussion

These findings expand research on the importance of grandparent–adult grandchild relationships and contribute to research on multigenerational relationships and health by considering how problems experienced by members of younger generations affect the psychological well-being of older adults.
The Relationship Between 10-Year Changes in Cognitive Control Beliefs and Cognitive Performance in Middle and Later Adulthood
Authors: Schiloski Kylie A , Lachman Margie E
Published: September 2024

Objectives

The present study used a cross-lagged panel design with longitudinal data to test if there is a reciprocal relationship between cognitive control beliefs and cognition (e.g., executive functioning and episodic memory) over 10 years, whether frequency of engaging in stimulating cognitive activities mediated this relationship, and if these relationships varied by age.

Methods

Data were collected as part of the second (M2, 2004–2005) and third (M3, 2013–2014) waves of the Midlife in the United States Study. The analysis sample included 2,532 participants with all variables at M2 and M3. Participants’ ages ranged from 33 to 83 (M = 54.92, standard deviation = 11.13) at M2.

Results

There was a reciprocal relationship between cognitive control beliefs and executive functioning. Higher executive functioning was related to greater maintenance of cognitive control beliefs for older, not younger, adults. Higher cognitive control beliefs were related to less decline in executive functioning. Though cognitive control beliefs predicted 10-year changes in episodic memory, the inverse relationship was not supported. Frequency of engaging in stimulating cognitive activities mediated the relationship between executive functioning and 10-year changes in cognitive control beliefs, but not cognitive control beliefs and 10-year changes in cognition.

Conclusions

Cognitive control beliefs are a promising mechanism to help protect against age-related declines in both executive functioning and episodic memory. Moreover, executive functioning also affects cognitive control beliefs. Specifically, those with higher executive functioning engage more frequently in stimulating cognitive activities, which helps maintain higher cognitive control beliefs.
A Pilot Randomized Controlled Trial to Examine the Impact of a Therapy Dog Intervention on Loneliness in Hospitalized Older Adults
Authors: Gee Nancy R , Townsend Lisa , Friedmann Erika , Barker Sandra B , Mueller Megan K
Published: September 2024

Background and Objectives

Loneliness is linked to significant health threats and is potentially more dangerous than obesity; it affects as many as 29% of noninstitutionalized older adults. Loneliness is exacerbated for those who require inpatient rehabilitation, are displaced from their social networks, spend little time receiving therapy, and are physically inactive and socially isolated. Emerging evidence suggests that companion animals provide a number of health and well-being benefits and that interacting with a trained therapy dog may reduce loneliness.

Research Design and Methods

Older adult (59+ years) medical inpatients (N = 42) were randomly assigned to receive 1 of 3 conditions: dog and handler interaction (animal-assisted interaction [AAI]), handler only conversational control (CC), or usual care (UC) for 20 min per day over 3 days. The UCLA Loneliness Scale (UCLA-LS) and Short Form (UCLA-SF) as well as an analog rating scale were used to assess loneliness. Linear mixed models with random intercepts were applied to examine differences in the changes from before to after the conditions.

Results

Changes in the UCLA-SF [t (200.356) = 1.851, p = .033] and the analog loneliness scale [t (194.407) = 2.651, p = .004], differed significantly between the AAI condition and the UC conditions but not between the CC and UC conditions (p = .175). Trajectories of changes in loneliness showed more improvement in the AAI than in the UC condition.

Discussion and Implications

These results indicate that AAI was effective for reducing loneliness in hospitalized older adults. Human handler only visits did not result in similar findings, indicating that there is something unique and beneficial about the presence of the dog.

Clinical Trial Registration

NCT05089201
Joint inversion of receiver function and surface wave dispersion based on the unscented Kalman inversion
Authors: Wang Longlong , Huang Daniel Zhengyu , Chen Yun , Liu Youshan , Du Nanqiao , Li Wei
Published: September 2024

Joint inversion, such as the combination of receiver function and surface wave dispersion, can significantly improve subsurface imaging by exploiting their complementary sensitivities. Bayesian methods have been demonstrated to be effective in this field. However, there are practical challenges associated with this approach. Notably, most Bayesian methods, such as the Markov Chain Monte Carlo method, are computationally intensive. Additionally, accurately determining the data noise across different data sets to ensure effective inversion is often a complex task. This study explores the unscented Kalman inversion (UKI) as a potential alternative. Through a data-driven approach to adjust estimated noise levels, we can achieve a balance between actual noise and the weights assigned to different data sets, enhancing the effectiveness of the inversion process. Synthetic tests of joint inversion of receiver function and surface wave dispersions indicate that the UKI can provide robust solutions across a range of data noise levels. Furthermore, we apply the UKI to real data from seismic arrays in Pamir and evaluate the accuracy of the joint inversion through posterior Gaussian distribution. Our results demonstrate that the UKI presents a promising supplement to conventional Bayesian methods in the joint inversion of geophysical data sets with superior computational efficiency.
Examining sustained sub-national health system development: experience from the Western Cape Province, South Africa, 1994–2016
Authors: Gilson Lucy , Vallabhjee Krishna , Naledi Tracey , Brady Leanne , Hawkridge Anthony , Pienaar David , Schneider Helen
Published: September 2024

Governance and leadership are recognized as central to health system development in low- and middle-income countries, yet few existing studies consider the influence of multilevel governance systems. South Africa is one of the many (quasi-)federal states. Provincial governments have responsibility for managing health care delivery within national policy frameworks and norms. The early post-apartheid period saw country-wide efforts to address the apartheid legacy of health system inequity and inefficiency, but health system transformation subsequently stalled in many provinces. In contrast, the Western Cape provincial health department sustained service delivery reform and strengthened management processes over the period 1994–2016. This department can be considered a ‘pocket of relative bureaucratic effectiveness’: an organizational entity that, compared to others, is relatively effective in carrying out its functions in pursuit of the public good. This paper considers what factors enabled the development of the Western Cape health system in the period 1994–2016. Two phases of data collection entailed document review, participatory workshops, 43 in-depth interviews with purposively selected key informants from inside and outside the Western Cape and a structured survey testing initial insights (response rate 42%). Analysis included triangulation across data sets, comparison between the Western Cape and other provincial experience and deeper reflection on these experiences drawing on POE theory and public administration literature. The analysis highlights the Western Cape experience of stable and astute sub-national governance and leadership and the deepening of administrative and technical capacity over time—within a specific provincial historical and political economy context that sustained the separation of political and administrative powers. Multilevel governance systems can create the space for sub-national POEs to emerge in their mediation of wider political economy forces, generating spaces for skilled reform leaders to act in the public interest, support the emergence of distributed leadership and develop robust management processes.
Compromised actin dynamics underlie the orofacial cleft in Baraitser-Winter Cerebrofrontofacial syndrome with a variant in ACTB
Authors: Tsujimoto Takayuki , Ou Yushi , Suzuki Makoto , Murata Yuka , Inubushi Toshihiro , Nagata Miho , Ishihara Yasuki , Yonei Ayumi , Miyashita Yohei , Asano Yoshihiro , Sakai Norio , Sakata Yasushi , Ogino Hajime , Yamashiro Takashi , Kurosaka Hiroshi
Published: September 2024

Craniofacial anomalies encompassing the orofacial cleft are associated with > 30% of systemic congenital malformations. Baraitser-Winter Cerebrofrontofacial syndrome (BWCFF) is a rare genetic disorder attributed to variants in the actin beta (ACTB) or actin gamma genes that are correlated with a range of craniofacial abnormalities, including cleft lip and/or palate. The underlying pathological mechanism of BWCFF remains elusive, and it is necessary to investigate the etiology of orofacial clefts in patients with BWCFF. In this study, we identified a missense variant (c.1043C > T: p.S348L) in the ACTB gene of a patient with BWCFF and concomitant cleft lip and palate. Furthermore, we performed functional assessments of this variant using various disease models such as the MDCK cell line and Xenopus laevis. These models revealed a compromised capacity of mutated ACTB to localize to the epithelial junction, consequently affecting the behavior of epithelial cells. Additionally, we discovered that the mutated ACTB exhibited an impaired ability to bind PROFILIN1, a critical factor in actin polymerization. This defective ability may contribute to the molecular etiology of aberrant epithelial cell adhesion and migration, resulting in orofacial cleft formation in BWCFF.
Small striatal huntingtin inclusions in patients with motor neuron disease with reduced penetrance and intermediate HTT gene expansions
Authors: Roos Anna-Karin , Stenvall Erica , Kockum Emmy Skelton , Grönlund Kornelia Åman , Alstermark Helena , Wuolikainen Anna , Andersen Peter M , Nordin Angelica , Forsberg Karin M E
Published: September 2024

Short tandem repeat expansions in the human genome are overrepresented in a variety of neurological disorders. It was recently shown that huntingtin (HTT) repeat expansions with full penetrance, i.e. 40 or more CAG repeats, which normally cause Huntington’s disease (HD), are overrepresented in patients with amyotrophic lateral sclerosis (ALS). Whether patients carrying HTT repeat expansions with reduced penetrance, (36–39 CAG repeats), or alleles with intermediate penetrance, (27–35 CAG repeats), have an increased risk of ALS has not yet been investigated. Here, we examined the role of HTT repeat expansions in a motor neuron disease (MND) cohort, searched for expanded HTT alleles, and investigated correlations with phenotype and neuropathology. MND patients harboring C9ORF72 hexanucleotide repeat expansions (HREs) were included, to investigate whether HTT repeat expansions were more common in this group. We found a high prevalence of intermediate (range 5.63%–6.61%) and reduced penetrance (range 0.57%–0.66%) HTT gene expansions in this cohort compared to other populations of European ancestry, but no differences between the MND cohort and the control cohort were observed, regardless of C9ORF72HRE status. Upon autopsy of three patients with intermediate or reduced penetrance HTT alleles, huntingtin inclusions were observed in the caudate nucleus and frontal lobe, but no significant somatic mosaicism was detected in different parts of the nervous system. Thus, we demonstrate, for the first time, huntingtin inclusions in individuals with MND and intermediate and reduced penetrance HTT repeat expansions but more clinicopathological investigations are needed to further understand the impact of HTT gene expansion-related pleiotropy.
Organizational structure and high-performance work practices
Authors: Eriksson Tor , Ortega Jaime
Published: September 2024

Using firm-level data from Denmark, a country characterized by a high level of adoption of “high-performance work practices” (HPWPs), we document a large percentage of firms with limited adoption and large differences depending on the firms’ organizational structures. To explain these differences, we propose a theoretical framework based on agency theory and on human resource process theory in which the benefits of HPWPs vary across organizations according to their organizational structure. We find that opportunity- and skill-enhancing practices are more frequently used in firms with a network structure than in firms with a divisional structure, which in turn use them more frequently than firms with a functional structure. These findings are consistent with the idea that firms whose structures are designed to rely more heavily on employee control benefit less from HPWPs than those whose structures are meant to promote employee commitment. The use of performance pay is greater in divisional firms than in functional firms, which is consistent with this same idea. However, we find that the use of performance pay is lower in network organizations than in divisional organizations and is not significantly different from its use in functional organizations.
Association between preoperative right heart catheterization parameters and outcomes in patients undergoing isolated coronary artery bypass grafting
Authors: Hameed Irbaz , Sulague Ralf Martz , Li Eric S , Yalcintepe Doruk , Candelario Katherine , Amabile Andrea , Effiom Victory B , Larson Haleigh , Geirsson Arnar , Williams Matthew L
Published: September 2024

Right ventricular catheterization may capture information that can help define prognosis before coronary artery bypass grafting (CABG). In this study, we evaluate the association between preoperative right heart catheterization parameters and outcomes of patients undergoing isolated CABG. All patients undergoing isolated CABG at our institution from 2013 to 2021 who also underwent preoperative right heart catheterization <14 days prior to isolated CABG were retrospectively queried. A total of 2343 patients underwent isolated CABG of whom 78 patients [20 (25.6%) female] were included in the final analysis. On multivariable regression, central venous pressure was significantly associated with operative mortality (odds ratio 1.14, 95% confidence interval 1.02–1.27, P = 0.024). Preoperative cardiac index was significantly inversely associated with intensive care unit length of stay (odds ratio 0.72, 95% confidence interval 0.62–0.84, P < 0.001) and duration of inotropic support (odds ratio 0.76, 95% confidence interval 0.63–0.92, P < 0.01). Assessment of preoperative cardiac function by right heart catheterization should be considered in high-risk patient populations, particularly those who have significant left ventricular dysfunction on preoperative echocardiography that would make them candidate for percutaneous coronary intervention, left ventricular assist device or heart transplantation. Further, right heart catheterization can help to guide preoperative optimization and intra-/postoperative decision-making.
The English Entries in Peter Simon Pallas’s Сравнительные Словари
Authors: Ó Fionnáin Mark
Published: September 2024

In the 1780s in Saint Petersburg there appeared a multilingual comparative dictionary, under the editorship of the German Peter Simon Pallas (1741–1811). Its title – ‘Comparative Vocabularies of All Languages and Dialects’ – illustrated its ambitious scope, and the first volume of this dictionary covered the languages of Europe, Asia and ‘the Islands of the Southern Ocean’. A second, promised, volume, containing the languages of Africa and the Americas, never appeared. For various reasons, this work, despite its vast linguistic content, has generally been discussed only briefly in the history of lexicography and linguistics in English, and the English entries themselves have not yet been presented in their entirety. The aim of this article is thus to correct this oversight, and to provide an overview of the history of the Vocabularies itself, as well as a list of the English entries as they appear in the work itself.
Postpartum thromboprophylaxis with enoxaparin: a prospective cohort study on patients’ adherence, injection experience, and information retention after counselling by pharmacists
Authors: Kho Boon Phiaw , Ho Hui Ting , Tan Shi Ying , Chee Fei San , Kow Fen Ting , Ooi Silvia , Kan Ying Min
Published: September 2024

Objectives

This research aimed to determine postpartum females’ self-reported adherence to and experience with short-term thromboprophylaxis using enoxaparin injection, after counselling by pharmacists. It also sought to assess their knowledge of thromboprophylaxis, injection techniques, and confidence in self-injecting.

Methods

This prospective cohort study was conducted at a public tertiary hospital in Malaysia from March to June 2023. Self-injection-naïve postpartum females who were initiated on thromboprophylaxis and counselled by a pharmacist were conveniently sampled. Knowledge regarding thromboprophylaxis, injection readiness, and technique were assessed one day after the counselling session. A telephonic interview was conducted at the end of the 10-day therapy to determine adherence and adverse effects experienced.

Key findings

A total of 259 subjects were successfully followed up, with 87.6% (n = 227) adherent to the therapy. Nonadherence was predominantly due to forgetfulness; four had their treatment withheld due to bleeding. One-third of subjects experienced localised pain and bruising. Subjects answered a median of 5/7 knowledge questions and recalled a median of 8/10 injection steps correctly, with those who read the information leaflet provided after counselling scoring significantly higher (P = .02). The majority declared moderate confidence in their ability to self-inject. Subjects who intended to self-inject (P < .01) and were more confident (P = .02) demonstrated better injection technique.

Conclusions

Postpartum females counselled by pharmacists largely adhered to short-term enoxaparin for thromboprophylaxis. The impact of the counselling session may be enhanced by addressing their psychological readiness to self-inject, awareness of adverse effects identification, mitigation, and management, as well as setting reminders to prevent forgetfulness to inject.
The Prime Geodesic Theorem in Arithmetic Progressions
Authors: Chatzakos Dimitrios , Harcos Gergely , Kaneko Ikuya
Published: September 2024

We address the prime geodesic theorem in arithmetic progressions and resolve conjectures of Golovchanskiĭ–Smotrov (1999). In particular, we prove that the traces of closed geodesics on the modular surface do not equidistribute in the reduced residue classes of a given modulus.
Evaluation of the Feasibility and Efficacy of Point-of-Care Antibody Tests for Biomarker-Guided Management of Coronavirus Disease 2019
Authors: Reilly Cavan , Mylonakis Eleftherios , Dewar Robin , Young Barnaby , Nordwall Jacqueline , Bhagani Sanjay , Chia Po-ying , Davis Ruby , Files Clark , Ginde Adit A , Hatlen Timothy , Helleberg Marie , Hayanga Awori , Jensen Tomas O , Jain Mamta K , Kalomenidis Ioannis , Kim Kami , Lallemand Perrine , Lindegaard Birgitte , Menon Anupama , Ognenovska Katherine , Poulakou Garyfallia , Thorup Røge Birgit , Rogers Angela J , Shaw-Saliba Katy , Sandkovsky Uriel , Trautner Barbara W , Vasudeva Shikha S , Vekstein Andrew , Viens Kimberley , Wyncoll James , DuChateau Brian , Zhang Zhenxing , Wu Shujiang , Babiker Abdel G , Davey Victoria , Gelijns Annetine , Higgs Elizabeth , Kan Virginia , Lundgren Jens , Matthews Gail V , Lane H Cliff
Published: September 2024

Background

Biomarker-guided therapy could improve management of inpatients with coronavirus disease 2019 (COVID-19). Although some results indicate that antibody tests are prognostic, little is known about patient management using point-of-care (POC) antibody tests.

Methods

COVID-19 inpatients were recruited to evaluate 2 POC tests: LumiraDx and RightSign. Ease of use data were collected. Blood was also collected for centralized testing using an established antibody assay (GenScript cPass). A nested case-control study assessed if POC tests conducted on stored specimens were predictive of time to sustained recovery, mortality, and a composite safety outcome.

Results

While both POC tests exhibited moderate agreement with the GenScript assay (both agreeing with 89% of antibody determinations), they were significantly different from the GenScript assay. Treating the GenScript assay as the gold standard, the LumiraDx assay had 99.5% sensitivity and 58.1% specificity whereas the RightSign assay had 89.5% sensitivity and 84.0% specificity. The LumiraDx assay frequently gave indeterminant results. Both tests were significantly associated with clinical outcomes.

Conclusions

Although both POC tests deviated moderately from the GenScript assay, they predicted outcomes of interest. The RightSign test was easier to use and was more likely to detect those lacking antibody compared to the LumiraDx test treating GenScript as the gold standard.

Clinical Trials Registration

NCT05227404.
Changes in Genital Human Papillomavirus (HPV) Prevalence During 12 Years of Girls-Only Bivalent HPV Vaccination: Results From a Biennial Repeated Cross-sectional Study
Authors: Kusters Johannes M A , Schim van der Loeff Maarten F , Heijne Janneke C M , King Audrey J , de Melker Hester E , Heijman Titia , Bogaards Johannes A , van Benthem Birgit H B ,   for the Papillomavirus Surveillance Among STI Clinic Youngsters in the Netherlands (PASSYON) Study Group, van der Meijden Helmie , Kampman Karlijn , Hoornenborg Elske , Bak Annet , Smit Marga , van Buel Harriette , Neienhuijsen Ferna , Ippel Marlot , Schriemer Dianne , Swart Inez , Twisk Denise
Published: September 2024

Background

Between 2009-2021, bivalent human papillomavirus (HPV) vaccination was offered to girls in the Netherlands. We studied the impact of girls-only HPV vaccination on genital HPV prevalence among young adults.

Methods

PASSYON (2009-2021) is a study among sexual health clinic clients aged 16–24 years old. Questionnaires elicited data on demographics, sexual behavior, and HPV vaccination status. Genital samples were analyzed using a PCR–based assay (SPF10-LiPA25). Prevalence trends of 12 high-risk genotypes were assessed as adjusted average annual change (aAAC), estimated using Poisson generalized estimating equations models. The relation between aAAC and phylogenetic distance to HPV-16/18 was assessed by means of regression and rank correlation analysis. Data were collected from 8889 females and 3300 heterosexual males (HMs).

Results

Among females (irrespective of vaccination status), prevalences of HPV-16/18/31/33/35/45 decreased significantly over time. Increasing trends were observed for HPV-39/52/56. Among both HMs and unvaccinated females (54.3%), HPV-16/18 significantly declined, as did HPV-31 among HMs. Contrastingly, HPV-52/58 increased significantly among HMs and unvaccinated females. The type-specific aAAC correlated well with the phylogenetic distance to HPV-16/18.

Conclusions

During 12 years of girls-only bivalent HPV vaccination in the Netherlands, decreasing trends of the vaccine types and cross-protected types were observed among females. Herd protection of vaccine types was observed for HMs and unvaccinated females, and 1 cross-protected type for HMs. Increasing prevalence trends of HPV types with large phylogenetic distance to the vaccine types might indicate type replacement.
Pharmacokinetics and safety of daptomycin administered subcutaneously in healthy volunteers: a single-blinded randomized crossover trial
Authors: Maurille Charles , Baldolli Aurélie , Creveuil Christian , Parienti Jean-Jacques , Michon Jocelyn , Peyro-Saint-Paul Laure , Brucato Sylvie , Dargere Sylvie , Comets Emmanuelle , Verdier Marie-Clémence , Verdon Renaud
Published: September 2024

Background

Daptomycin stands as a key IV antibiotic in treating MRSA infections. However, patients facing challenges with difficult venous access require alternative administration routes. This study aimed to evaluate the pharmacokinetic (PK) profile and safety of subcutaneous (SC) daptomycin.

Patients and methods

In a two-period, two-treatment, single-blind crossover Phase I trial (ClinicalTrials.gov NCT04434300), participants with no medical history received daptomycin (10 mg/kg) both IV and SC in a random order, with a minimum 2 week washout period together with matched placebo (NaCl 0.9%). Blood samples collected over 24 h facilitated PK comparison. Monte Carlo simulations assessed the PTA for various dosing regimens. Adverse events were graded according to Common Terminology Criteria for Adverse Events(CTCAE) v5.0.

Results

Twelve participants (aged 30.9 ± 24.4 years; 9 male,75%) were included. SC daptomycin exhibited delayed (median Tmax 0.5 h for IV versus 4 h for SC) and lower peak concentration than IV (Cmax = 132.2 ± 16.0 μg/mL for IV versus 57.3 ± 8.6 μg/mL for SC; P < 0.001). SC AUC0–24 (937.3 ± 102.5 μg·h/mL) was significantly lower (P = 0.005) than IV AUC0–24 (1056.3 ± 123.5 μg·h/mL) but was deemed bioequivalent. PTA demonstrated target AUC0–24 attainment for 100% of simulated individuals, for both 8 and 10 mg/kg/24 h SC regimens. Adverse events (AEs) related to SC daptomycin were more frequent than for SC placebo (25 versus 13, P = 0.016). No serious AEs were reported.

Conclusions

Single-dose SC daptomycin infusion proved to be safe, exhibiting a bioequivalent AUC0–24 compared with the IV route. The SC route emerges as a potential and effective alternative when IV administration is not possible.
Phage susceptibility testing methods or ‘phagograms’: where do we stand and where should we go?
Authors: Kolenda Camille , Jourdan Julie , Roussel-Gaillard Tiphaine , Medina Mathieu , Laurent Frédéric
Published: September 2024

Phage therapy is a highly promising approach to address the challenge that is presented by the global burden of antimicrobial resistance. Given the natural specificity of phages, phage susceptibility testing (PST) is a prerequisite for successful personalized therapy, allowing the selection of active phages from large and diverse collections. However, the issue of an easy-to-use and standardized technique remains. In this review, we describe the principles, advantages and drawbacks of two routinely used PST techniques: plaque and growth kinetic assays. These are labour-intensive and time-consuming methods that require automation of one or more steps, including preparation of test panels, incubation, reading and analysis of results. In addition to automation, there is an urgent need to establish a reference method to enable efficient of PST techniques selection of therapeutic phages. We discuss knowledge gaps and parameters that need to be investigated to work towards this goal.
270 Prenatal stress programming: Impact on dam and offspring immune phenotype and performance
Authors: Hernandez Lily P , Main Alexis R H , Salak-Johnson Janeen L
Published: September 2024

Maternal stress during critical periods of fetal development is linked to the modified expression of several physiological processes. Despite attempts to minimize chronic stress and enhance sow well-being, some animals still experience stress, which can have short and long-term effects on future progeny. Therefore, we evaluated the impact of maternal stress on the immune phenotype and performance of pregnant gilts who had experienced pre- and post-natal stress and whether their offspring were affected. A total of 11 primiparous females (201.32 ± 17.18 kg at farrowing) clustered into treatment groups based on the treatment of their dams were used in this study. Their dams had been randomly allotted to receive either a placebo (CON) or Hydrocortisone Acetate capsules twice per day for 21 d during either mid (MID; d 51 to 72) or late (LATE; d 81 to 102) gestation. Prenatally stressed dams were sampled on gestational d 45, 60, 75, and 105 to determine descriptive and functional immune analysis. Productivity measures were assessed, including farrowing duration and the interval between piglets. Blood samples were taken from a subset of piglets born to these dams on d 7, 14, and 21 of lactation and then 24 h, 7, and 14 d post-wean. Data were analyzed using the Mixed procedure of SAS with repeated measures. Numbers of lymphocytes were elevated in gilts from LATE-treated dams compared with those from MID or CON dams for the entire study period (P < 0.05). All other descriptive immune measures, including neutrophil-to-lymphocyte ratio, were not different between groups during the gestational period. Mitogen-induced lymphocyte proliferation did not differ across treatments for prenatally stressed dams. No maternal treatment effects for any litter traits, farrowing duration, or interval between each piglet, but there was a tendency (P < 0.10) for piglets born to MID-stressed dams to be heavier than those born to CON dams. Total lymphocyte numbers were least in the progeny of MID-treated dams compared with piglets from LATE and CON dams for the entire lactation period. Over time, progeny from LATE-treated gilts had a more stimulated B-cell proliferation index during lactation (P < 0.05). Conversely, Concanavalin-A-induced lymphocyte proliferation tended to be least in offspring from MID-treated dams compared with CON. They also tended to have less percentage and numbers of lymphocytes than offspring from LATE and CON dams for the entire post-wean period. The offspring from MID-treated dams also had the greatest (P < 0.05) neutrophil-to-lymphocyte ratio for the entire period. While prenatal stress had minimal impact on the immune expression of the dam, its influence was evident in their progeny, particularly with MID. Results indicate that the programming effects may only be apparent in later generations. The study also suggests that mid-gestation is a more sensitive period for maternal stress in fetal development.
424 Examining the effect of genetics between Bos taurus and Bos Indicus influenced cattle on production performance, carcass characteristics, and feeding behavior
Authors: Okamoto Lillian , Stegemiller Morgan R , Reichhardt Caleb C , Alberto Anthony F , Bayles Sarah A , Roholt Bryce W , Murdoch Brenda M , Thornton-Kurth Kara J
Published: September 2024

Cattle production within the US has and will continue to be negatively impacted by climate change. With the amount of natural resources and arable land decreasing every day, it is imperative to improve cattle production efficiency to meet the needs of the rapidly growing global population. Increasing the percentage of Bos indicus (BI) genetics within the US beef herd is one potential method of doing so, as BI cattle are better adapted to nutritional stress and increment weather when compared with Bos taurus (BT) cattle. Despite these positive attributes, BI cattle often have a more excitable temperament, exhibit decreased production performance, and have compromised carcass quality when compared with BT cattle. The objective of this study was to examine how breed type and genetic differences between BT and BT-BI crossbred cattle contribute to production performance, feeding behavior, and carcass quality in a temperate climate setting. This study utilized a total of 88 steers of two different breed types, Angus (AN; 100% BT) and Santa Gertrudis influenced (SG; 19% BI, 81% BT), and took place over 2 yr in 2020 (n = 23 AN and n = 9 SG) and 2021 (n = 35 AN and n = 21 SG). All steers were fed a typical feedlot ration, were housed in pens equipped with Vytelle units, and were harvested at a commercial facility once industry backfat standards were achieved. Statistical analysis was conducted using the Mixed Procedure of SAS with Tukey-Kramer adjustments. Production-related traits including dry matter intake (DMI), average daily gain (ADG), and feed efficiency (G:F) were not affected (P > 0.10) by breed type. Intramuscular fat was increased (P = 0.0003) in AN steers; however, other carcass traits including ribeye fat thickness, hot carcass weight (HCW), cold camera ribeye size, and cold camera yield grade were unaffected (P > 0.10) by breed type. Feeding behavior traits including the number and duration of bunk visits (BV) and feed bouts (FB) did not differ (P > 0.10) between breeds, but SG steers did spend more time with their heads down during such BV (P = 0.0047) and FB (P = 0.0078), respectively. To better examine the genomic differences between the two beef breeds, a Bovine GGP 100k assay was completed commercially and data were analyzed using models in SNP and Variation Suite. Following FDR corrections, SNPs with differences in allelic combinations that contributed to statistical significance were observed in ADG, DMI, HCW, marbling scores, and duration of BV and FB where the steers had their heads down. Potential breed effects were observed in marbling scores, cold camera yield grade, and cold camera ribeye size, however, due to the limited number of steers, additional research utilizing a larger population is warranted to validate such findings.