An international breeding project using a wild potato relative Solanum commersonii resulted in two new frost-tolerant native potato cultivars for the Andes and the Altiplano.

This breeding project, initiated at the United States Potato Genebank (USPG) in collaboration with Peruvian partners Instituto Nacional de Innovacion Agraria (INIA), International Potato Center, Peru (CIP), and local farmers, sought to enhance cold hardiness and frost tolerance in native potato cultivars in Peru. The Andes and Altiplano are often affected by frost, which causes significant reduction in yield; creating varieties with superior resilience is a critical undertaking. The goal was to transfer outstanding non-acclimated cold tolerance and acclimation capacity found in wild potato species Solanum commersonii (cmm). Breeding families segregating for cold hardiness were created using (a) a somatic hybrid cmm + haploid Solanum tuberosum (tbr) (cv. Superior, US variety from Wisconsin) as male and (b) seven cultivars native to Peru of the species S. tuberosum sbsp. andigenum (adg) as females. All plant materials were part of the USPG germplasm collection. Sexual seeds of each family were sent to Peru for evaluations under the natural conditions of the Andean highlands and Altiplano. The plants were assessed for their response to frost, and genotypes showing exceptional tolerance were selected. Plants were also evaluated for good tuber traits and yield. Initial planting involving ~2,500 seedlings in five locations resulted in selecting 58 genotypes with exceptional frost tolerance, good recovery capacity after frost, and good tuber traits. Over the years, evaluations continued and were expanded to replicated field trials in the harsher conditions of the Altiplano (Puno). All trials confirmed consistency of frost tolerance over time and location, tuber quality, and yield. After 8 years, two advanced clones were considered for cultivar release because of their exceptional frost tolerance and superior field productivity that outyielded many of the established cultivars in the region. In November 2018, a new native cultivar named Wiñay, a Quechua word meaning "to grow" was released in Peru. In 2022, a second cultivar followed with the name Llapanchispaq (meaning "for all of us"). This project evidenced that a multinational and all-encompassing approach to deploy valuable genetic diversity can work and deliver effective results. This is even more significant when outcomes can promote food security and sustainability in very vulnerable regions of the world.

High-grade prostate cancer demonstrates preferential growth in the cranio-caudal axis and provides discrimination of disease grade in an MRI parametric model.

OBJECTIVES: To determine if multiparametric MRI prostate cancer (PC) lesion dimensions in different axes could distinguish between PC, grade group (GG) >2, and GG >3 on targeted transperineal biopsy and create and validate a predictive model on a separate cohort. METHODS: The maximum transverse, anterio-posterior, and cranio-caudal lesion dimensions were assessed against the presence of any cancer, GG >2, and GG >3 on biopsy by binary logistic regression. The optimum multivariate models were evaluated on a separate cohort. RESULTS: One hundred and ninety-three lesions from 148 patients were evaluated. Increased lesion volume, Prostate Specific Antigen (PSA), Prostate Imaging Reporting and Data System score, and decreased Apparent Diffusion Coefficient (ADC) were associated with increased GG (P < .001). The ratio of cranio-caudal to anterior-posterior lesion dimension increased from 1.20 (95% CI, 1.14-1.25) for GG ≤ 3 to 1.43 (95% CI, 1.28-1.57) for GG > 3 (P = .0022). The cranio-caudal dimension of the lesion was the strongest predictor of GG >3 (P = .000, area under the receiver operator characteristic curve [AUC] = 0.81). The best multivariate models had an AUC of 0.84 for cancer, 0.88 for GG > 2, and 0.89 for GG > 3. These models were evaluated on a separate cohort of 40 patients with 61 lesions. They demonstrated an AUC, sensitivity, and specificity of 0.82, 82.3%, and 55.5%, respectively, for the detection of cancer. For GG > 2, the models achieved an AUC of 0.84, sensitivity of 91.7%, and specificity of 69.4%. Additionally, for GG > 3, the models showed an AUC of 0.92, sensitivity of 88.9%, and specificity of 98.1%. CONCLUSIONS: Cranio-caudal lesion dimension when used in conjunction with other parameters can create a model superior to the Prostate Imaging Reporting and Data Systems score in predicting cancer. ADVANCES IN KNOWLEDGE: Higher-grade PC has a propensity to grow in the cranio-caudal direction, and this could be factored into MRI-based predictive models of prostate biopsy grade.

The use of technology to address loneliness and social isolation among older adults: the role of social care providers.

BACKGROUND: Addressing loneliness and social isolation among older adults remains a public health priority. The restrictions enforced during the COVID-19 pandemic simultaneously heightened the need for services to overcome social isolation and reduce loneliness among older adults, while also limiting social care providers' ability to deliver these. The aim of this study was to explore the experiences of social care providers in using technology to address loneliness and social isolation among older adults during the pandemic. METHODS: This was a mixed methods study involving an online survey and interviews with providers of older adult social care in Wales, UK. Invitations to participate were sent to commissioners and providers of adult social care services, including those working in the voluntary and community sectors, across all local authorities in Wales. Data was collected between September 2021 and January 2022. RESULTS: Sixty-one service providers completed the survey, 19 of whom also took part in an interview. Addressing loneliness and isolation among older adults was reported as a key concern by nearly all survey respondents. While telephone calls were the most common means of facilitating social interaction, many service providers also tried to support older adults to make more use of devices that they already had (e.g., smartphones to hold video calls). Where funding was available, organisations purchased devices, such as tablets and smart speakers, for older adults. Analysis of interviews resulted in three themes: (1) The potential and limitations of technology; (2) Individuals' capabilities, confidence, motivations and values; and (3) The wider system. CONCLUSIONS: Technology was employed in a variety of ways during the pandemic to address loneliness and social isolation among older adults; many service providers continue to use technology in a hybrid system of care now that pandemic-related social restrictions have been lifted. Our findings emphasise a need for technology-assisted interventions to be designed and deployed in alignment with service users' values, motivations and capabilities. Further, there is a need to better support service providers to assess loneliness and social isolation among older adults, and to acknowledge the important role providers play in helping older adults to adopt technology-assisted interventions.

Quantifying unmet need in General Practice: a retrospective cohort study of administrative data.

OBJECTIVES: To assess whether patients attending general practices (GPs) in socioeconomically (SE) deprived areas receive the same amount of care, compared with similar patients (based on age, sex and level of morbidity) attending GPs in less deprived areas. If not, to quantify the additional resource that would be required by GPs in deprived areas to achieve parity. DESIGN: Retrospective cohort study. SETTING: 150 GPs in Scotland, UK, divided into two groups: 80 practices in Scottish Index of Multiple Deprivation (SIMD) deciles 1-5 (more SE deprived); 70 practices in SIMD deciles 6-10 (less SE deprived). PATIENTS: 437 590 patients registered with a more SE deprived GP, and 333 994 patients registered with a less SE deprived GP, for the whole study period (2013-2016), who made at least one appointment. OUTCOMES: The number of contacts and total contact time between patients and clinical staff. RESULTS: Patients in more SE deprived areas had slightly more discrete contacts over 3 years (11.8 vs 11.4), but each patient had marginally less contact time (146.1 vs 149.5 min). Stratified by sex and age, differences were also small. Stratified by the number of long-term conditions (LTCs), practices in more SE deprived areas delivered significantly less contact time than practices in less SE deprived areas. Over 3 years, 8 fewer minutes for patients with no LTCs, and 24, 27, 38 and 28 fewer minutes for patients with 1, 2, 3-4 or 5+LTCs, respectively. CONCLUSION: If GPs in more SE deprived areas were to give an equal amount of direct contact time to patients with the same level of need served by GPs in less SE deprived areas, this would require a 14% increase in patient contact time. This represents a significant unmet need, supporting the case for redistribution of resources to tackle the inverse care law.

Leptospirosis in the Air: A Case Review Series During Air Medical Transport in Haiti.

Leptospirosis is an infectious illness encountered mostly in tropical climates and has been of particular concern in Haiti after natural disasters. Heavy rainfalls and natural disasters in combination with scarce resources to control and identify clusters of infections make certain populations and countries vulnerable. In some cases, patients who contract this disease may need air medical transport to hospitals that have a higher level of care. In this case report, a trio of cases is highlighted from an outbreak that required air transport to transfer patients to a facility with the availability of an intensive care unit. The goal of highlighting these cases is to increase the awareness of physicians and air transport providers to the manifestation and treatment of this disease and to provide pearls to stabilize patients during transport.

Pangenome analyses reveal impact of transposable elements and ploidy on the evolution of potato species.

Potato (Solanum sp., family Solanaceae) is the most important noncereal food crop globally. It has over 100 wild relatives in the Solanum section Petota, which features species with both sexual and asexual reproduction and varying ploidy levels. A pangenome of Solanum section Petota composed of 296 accessions was constructed including diploids and polyploids compared via presence/absence variation (PAV). The Petota core (genes shared by at least 97% of the accessions) and shell genomes (shared by 3 to 97%) are enriched in basic molecular and cellular functions, while the cloud genome (genes present in less than 3% of the member accessions) showed enrichment in transposable elements (TEs). Comparison of PAV in domesticated vs. wild accessions was made, and a phylogenetic tree was constructed based on PAVs, grouping accessions into different clades, similar to previous phylogenies produced using DNA markers. A cladewise pangenome approach identified abiotic stress response among the core genes in clade 1+2 and clade 3, and flowering/tuberization among the core genes in clade 4. The TE content differed between the clades, with clade 1+2, which is composed of species from North and Central America with reproductive isolation from species in other clades, having much lower TE content compared to other clades. In contrast, accessions with in vitro propagation history were identified and found to have high levels of TEs. Results indicate a role for TEs in adaptation to new environments, both natural and artificial, for Solanum section Petota.

Hearing of malaria mosquitoes is modulated by a beta-adrenergic-like octopamine receptor which serves as insecticide target.

Malaria mosquitoes acoustically detect their mating partners within large swarms that form transiently at dusk. Indeed, male malaria mosquitoes preferably respond to female flight tones during swarm time. This phenomenon implies a sophisticated context- and time-dependent modulation of mosquito audition, the mechanisms of which are largely unknown. Using transcriptomics, we identify a complex network of candidate neuromodulators regulating mosquito hearing in the species Anopheles gambiae. Among them, octopamine stands out as an auditory modulator during swarm time. In-depth analysis of octopamine auditory function shows that it affects the mosquito ear on multiple levels: it modulates the tuning and stiffness of the flagellar sound receiver and controls the erection of antennal fibrillae. We show that two α- and ß-adrenergic-like octopamine receptors drive octopamine's auditory roles and demonstrate that the octopaminergic auditory control system can be targeted by insecticides. Our findings highlight octopamine as key for mosquito hearing and mating partner detection and as a potential novel target for mosquito control.

Towards clinical applicability and computational efficiency in automatic cranial implant design: An overview of the AutoImplant 2021 cranial implant design challenge.

Cranial implants are commonly used for surgical repair of craniectomy-induced skull defects. These implants are usually generated offline and may require days to weeks to be available. An automated implant design process combined with onsite manufacturing facilities can guarantee immediate implant availability and avoid secondary intervention. To address this need, the AutoImplant II challenge was organized in conjunction with MICCAI 2021, catering for the unmet clinical and computational requirements of automatic cranial implant design. The first edition of AutoImplant (AutoImplant I, 2020) demonstrated the general capabilities and effectiveness of data-driven approaches, including deep learning, for a skull shape completion task on synthetic defects. The second AutoImplant challenge (i.e., AutoImplant II, 2021) built upon the first by adding real clinical craniectomy cases as well as additional synthetic imaging data. The AutoImplant II challenge consisted of three tracks. Tracks 1 and 3 used skull images with synthetic defects to evaluate the ability of submitted approaches to generate implants that recreate the original skull shape. Track 3 consisted of the data from the first challenge (i.e., 100 cases for training, and 110 for evaluation), and Track 1 provided 570 training and 100 validation cases aimed at evaluating skull shape completion algorithms at diverse defect patterns. Track 2 also made progress over the first challenge by providing 11 clinically defective skulls and evaluating the submitted implant designs on these clinical cases. The submitted designs were evaluated quantitatively against imaging data from post-craniectomy as well as by an experienced neurosurgeon. Submissions to these challenge tasks made substantial progress in addressing issues such as generalizability, computational efficiency, data augmentation, and implant refinement. This paper serves as a comprehensive summary and comparison of the submissions to the AutoImplant II challenge. Codes and models are available at https://github.com/Jianningli/Autoimplant_II.

Eyes on Topical Ocular Disposition: The Considered Design of a Lead Janus Kinase (JAK) Inhibitor That Utilizes a Unique Azetidin-3-Amino Bridging Scaffold to Attenuate Off-Target Kinase Activity, While Driving Potency and Aqueous Solubility.

An unmet medical need remains for patients suffering from dry eye disease (DED). A fast-acting, better-tolerated noncorticosteroid anti-inflammatory eye drop could improve patient outcomes and quality of life. Herein, we describe a small-molecule drug discovery effort to identify novel, potent, and water-soluble JAK inhibitors as immunomodulating agents for topical ocular disposition. A focused library of known 3-(4-(2-(arylamino)pyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitriles was evaluated as a molecular starting point. Structure-activity relationships (SARs) revealed a ligand-efficient (LE) JAK inhibitor series, amenable to aqueous solubility. Subsequent in vitro analysis indicated the potential for off-target toxicity. A KINOMEscan selectivity profile of 5 substantiated the likelihood of widespread series affinity across the human kinome. An sp2-to-sp3 drug design strategy was undertaken to attenuate off-target kinase activity while driving JAK-STAT potency and aqueous solubility. Tactics to reduce aromatic character, increase fraction sp3 (Fsp3), and bolster molecular complexity led to the azetidin-3-amino bridging scaffold in 31.

Umbrella systematic review finds limited evidence that school absence explains the association between chronic health conditions and lower academic attainment.

Introduction: Absence from school is more frequent for children with chronic health conditions (CHCs) than their peers and may be one reason why average academic attainment scores are lower among children with CHCs. Methods: We determined whether school absence explains the association between CHCs and academic attainment through a systematic review of systematic reviews of comparative studies involving children with or without CHCs and academic attainment. We extracted results from any studies that tested whether school absence mediated the association between CHCs and academic attainment. Results: We identified 27 systematic reviews which included 441 unique studies of 7, 549, 267 children from 47 jurisdictions. Reviews either covered CHCs generally or were condition-specific (e.g., chronic pain, depression, or asthma). Whereas reviews found an association between a range of CHCs (CHCs generally, cystic fibrosis, hemophilia A, end-stage renal disease (pre-transplant), end-stage kidney disease (pre-transplant), spina bifida, congenital heart disease, orofacial clefts, mental disorders, depression, and chronic pain) and academic attainment, and though it was widely hypothesized that absence was a mediator in these associations, only 7 of 441 studies tested this, and all findings show no evidence of absence mediation. Conclusion: CHCs are associated with lower academic attainment, but we found limited evidence of whether school absence mediates this association. Policies that focus solely on reducing school absence, without adequate additional support, are unlikely to benefit children with CHCs. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=285031, identifier: CRD42021285031.

Examining safety and efficacy of a fixed concentration heparin dosing strategy for anticoagulation in neonatal extracorporeal membrane oxygenation.

OBJECTIVES: The paediatric intensive care unit changed heparin infusion dosing from a variable weight-based concentration to a fixed concentration strategy, when smart pump-based drug library was introduced. This change meant significantly lower rates of infusion were needed for the same dose of heparin in the neonatal population. We performed a safety and efficacy assessment of this change. METHODS: We performed a retrospective single-centre evaluation based on data from respiratory VA-extracorporeal membrane oxygenation (ECMO) patients weighing ≤5 kg, pre and post the change to fixed strength heparin infusion. Efficacy was analysed by distribution of activated clotting times (ACT) and heparin dose requirements between the groups. Safety was analysed using thrombotic and haemorrhagic event rates. Continuous variables were reported as median, interquartile ranges, and non-parametric tests were used. Generalised estimating equations (GEE) were used to analyse associations of heparin dosing strategy with ACT and heparin dose requirements in the first 24 h of ECMO. Incidence rate ratios of circuit related thrombotic and haemorrhagic events between groups were analysed using Poisson regression with offset for run hours. RESULTS: 33 infants (20 variable weight-based, 13 fixed concentration) were analysed. Distribution of ACT ranges and heparin dose requirements were similar between the two groups during the ECMO run and this was confirmed by GEE. Incidence rate ratios of thrombotic (fixed v weight-based) (1.9 [0.5-8], p = .37), and haemorrhagic events (0.9 [0.1-4.9], p = .95) did not show statistically significant differences. CONCLUSIONS: Fixed concentration dosing of heparin was at least equally effective and safe compared to a weight-based dosing.

The auditory efferent system in mosquitoes.

Whilst acoustic communication forms an integral component of the mating behavior of many insect species, it is particularly crucial for disease-transmitting mosquitoes; swarming males rely on hearing the faint sounds of flying females for courtship initiation. That males can hear females within the din of a swarm is testament to their fabulous auditory systems. Mosquito hearing is highly frequency-selective, remarkably sensitive and, most strikingly, supported by an elaborate system of auditory efferent neurons that modulate the auditory function - the only documented example amongst insects. Peripheral release of octopamine, serotonin and GABA appears to differentially modulate hearing across major disease-carrying mosquito species, with receptors from other neurotransmitter families also identified in their ears. Because mosquito mating relies on hearing the flight tones of mating partners, the auditory efferent system offers new potential targets for mosquito control. It also represents a unique insect model for studying auditory efferent networks. Here we review current knowledge of the mosquito auditory efferent system, briefly compare it with its counterparts in other species and highlight future research directions to unravel its contribution to mosquito auditory perception.

Survivability of locally prepared versus imported Descemet membrane endothelial keratoplasty grafts in Edmonton.

OBJECTIVE: This study aimed to evaluate the long-term graft survivability of locally prestripped versus imported prestripped Descemet membrane endothelial keratoplasty (DMEK) grafts in Edmonton. DESIGN: Prospective cohort study of patients who underwent DMEK surgery between January 1, 2020, and December 31, 2020. PARTICIPANTS: All patients receiving a DMEK transplant during the study period in Edmonton. METHODS: Two local technicians were trained to prestrip DMEK grafts in Edmonton. When available, local tissue was prestripped for DMEK surgery; otherwise, prestripped DMEK grafts were imported from an accredited American eye bank. Patient characteristics and DMEK graft characteristics and DMEK survivability were evaluated and compared between the 2 groups. RESULTS: Thirty-two locally prestripped DMEK grafts and 35 imported prestripped DMEK grafts were used during the study period. Donor cornea characteristics and patient characteristics were similar between the 2 groups. Best-corrected visual acuity improved up to 6 months postoperatively and was 0.2 logMAR in the locally prestripped DMEK group and 0.2 logMAR in the imported DMEK group (p = 0.56). Rebubble rates were 25% in the locally prestripped DMEK group and 19% in the imported DMEK group (p = 0.43). There was 1 primary graft failure in each group (p = 0.93). Endothelial cell density decreased by 37% in the locally prestripped DMEK group and by 33% in the imported DMEK group 2 years after transplantation. CONCLUSIONS: The long-term survivability of locally prepared DMEK grafts is comparable with that of DMEK grafts imported from American eye banks.

Collecting wild potato species (Solanum sect. Petota) in Peru to enhance genetic representation and fill gaps in ex situ collections.

Crop wild relatives (CWRs) are important sources of novel genes, due to their high variability of response to biotic and abiotic stresses, which can be invaluable for crop genetic improvement programs. Recent studies have shown that CWRs are threatened by several factors, including changes in land-use and climate change. A large proportion of CWRs are underrepresented in genebanks, making it necessary to take action to ensure their long-term ex situ conservation. With this aim, 18 targeted collecting trips were conducted during 2017/2018 in the center of origin of potato (Solanum tuberosum L.), targeting 17 diverse ecological regions of Peru. This was the first comprehensive wild potato collection in Peru in at least 20 years and encompassed most of the unique habitats of potato CWRs in the country. A total of 322 wild potato accessions were collected as seed, tubers, and whole plants for ex situ storage and conservation. They belonged to 36 wild potato species including one accession of S. ayacuchense that was not conserved previously in any genebank. Most accessions required regeneration in the greenhouse prior to long-term conservation as seed. The collected accessions help reduce genetic gaps in ex situ conserved germplasm and will allow further research questions on potato genetic improvement and conservation strategies to be addressed. These potato CWRs are available by request for research, training, and breeding purposes under the terms of the International Treaty for Plant Genetic Resources for Food and Agriculture (ITPGRFA) from the Instituto Nacional de Innovacion Agraria (INIA) and the International Potato Center (CIP) in Lima-Peru.

The Spectrum of MORC2-Related Disorders: A Potential Link to Cockayne Syndrome.

BACKGROUND: Cockayne syndrome (CS) is a DNA repair disorder primarily associated with pathogenic variants in ERCC6 and ERCC8. As in other Mendelian disorders, there are a number of genetically unsolved CS cases. METHODS: We ascertained five individuals with monoallelic pathogenic variants in MORC2, previously associated with three dominantly inherited phenotypes: an axonal form of Charcot-Marie-Tooth disease type 2Z; a syndrome of developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy; and a rare form of spinal muscular atrophy. RESULTS: One of these individuals bore a strong phenotypic resemblance to CS. We then identified monoallelic pathogenic MORC2 variants in three of five genetically unsolved individuals with a clinical diagnosis of CS. In total, we identified eight individuals with MORC2-related disorder, four of whom had clinical features strongly suggestive of CS. CONCLUSIONS: Our findings indicate that some forms of MORC2-related disorder have phenotypic similarities to CS, including features of accelerated aging. Unlike classic DNA repair disorders, MORC2-related disorder does not appear to be associated with a defect in transcription-coupled nucleotide excision repair and follows a dominant pattern of inheritance with variants typically arising de novo. Such de novo pathogenic variants present particular challenges with regard to both initial gene discovery and diagnostic evaluations. MORC2 should be included in diagnostic genetic test panels targeting the evaluation of microcephaly and/or suspected DNA repair disorders. Future studies of MORC2 and its protein product, coupled with further phenotypic characterization, will help to optimize the diagnosis, understanding, and therapy of the associated disorders.

Cost-effectiveness of locally prepared Descemet membrane endothelial keratoplasty grafts in Edmonton.

OBJECTIVE: This study aimed to show the cost-effective benefits of creating a sustainable local program where Descemet membrane endothelial keratoplasty (DMEK) grafts were prepared locally instead of imported from American eye banks. DESIGN: Retrospective observational study. METHODS: In 2018, 2 local technicians were trained to prestrip DMEK grafts in Edmonton up to 2 days before surgery when local donor tissue was available. When no local tissue was available, prestripped DMEK grafts were imported from U.S. eye banks. The total cost of locally prepared and imported DMEK grafts over 27 months was compared with the cost that otherwise would have been accrued if all DMEK grafts had been imported. RESULTS: Over 27 months, 82 DMEK grafts (55.3%) were prepared locally and 63 DMEK grafts (44.7%) were imported. The total cost of preparing 82 grafts locally was $9349.19. The total cost of importing 63 prestripped DMEK grafts was $282 431.52. The combined total cost of locally prepared and imported DMEK grafts was $291 780.71. The total cost that otherwise would have been incurred if every graft was imported was $632 108.64. This difference in costs was $340 327.93 over 27 months. CONCLUSIONS: Establishing a sustainable program to make high-quality DMEK grafts with local donor corneas is a cost-effective alternative to importing prestripped DMEK grafts in Edmonton.

Composite Indium Tin Oxide Nanofibers with Embedded Hematite Nanoparticles for Photoelectrochemical Water Splitting.

Hematite is a classical photoanode material for photoelectrochemical water splitting due to its stability, performance, and low cost. However, the effect of particle size is still a question due to the charge transfer to the electrodes. In this work, we addressed this subject by the fabrication of a photoelectrode with hematite nanoparticles embedded in close contact with the electrode substrate. The nanoparticles were synthesized by a solvothermal method and colloidal stabilization with charged hydroxide molecules, and we were able to further use them to prepare electrodes for water photo-oxidation. Hematite nanoparticles were embedded within electrospun tin-doped indium oxide nanofibers. The fibrous layer acted as a current collector scaffold for the nanoparticles, supporting the effective transport of charge carriers. This method allows better contact of the nanoparticles with the substrate, and also, the fibrous scaffold increases the optical density of the photoelectrode. Electrodes based on nanofibers with embedded nanoparticles display significantly enhanced photoelectrochemical performance compared to their flat nanoparticle-based layer counterparts. This nanofiber architecture increases the photocurrent density and photon-to-current internal conversion efficiency by factors of 2 and 10, respectively.