Definition of the Post-COVID syndrome using a symptom-based Post-COVID score in a prospective, multi-center, cross-sectoral cohort of the German National Pandemic Cohort Network (NAPKON).

PURPOSE: The objective examination of the Post-COVID syndrome (PCS) remains difficult due to heterogeneous definitions and clinical phenotypes. The aim of the study was to verify the functionality and correlates of a recently developed PCS score. METHODS: The PCS score was applied to the prospective, multi-center cross-sectoral cohort (in- and outpatients with SARS-CoV-2 infection) of the "National Pandemic Cohort Network (NAPKON, Germany)". Symptom assessment and patient-reported outcome measure questionnaires were analyzed at 3 and 12 months (3/12MFU) after diagnosis. Scores indicative of PCS severity were compared and correlated to demographic and clinical characteristics as well as quality of life (QoL, EQ-5D-5L). RESULTS: Six hundred three patients (mean 54.0 years, 60.6% male, 82.0% hospitalized) were included. Among those, 35.7% (215) had no and 64.3% (388) had mild, moderate, or severe PCS. PCS severity groups differed considering sex and pre-existing respiratory diseases. 3MFU PCS worsened with clinical severity of acute infection (p = .011), and number of comorbidities (p = .004). PCS severity was associated with poor QoL at the 3MFU and 12MFU (p < .001). CONCLUSION: The PCS score correlated with patients' QoL and demonstrated to be instructive for clinical characterization and stratification across health care settings. Further studies should critically address the high prevalence, clinical relevance, and the role of comorbidities. TRAIL REGISTRATION NUMBER: The cohort is registered at www. CLINICALTRIALS: gov under NCT04768998.

Genetic dissection of early-season cold tolerance in sorghum: genome-wide association studies for seedling emergence and survival under field and controlled environment conditions.

KEY MESSAGE: A QTL on sorghum chromosome SBI-06 putatively improves field emergence under low-temperature conditions. Low temperatures decisively limit seedling emergence and vigor during early growth of sorghum and, thus, strongly impair geographical expansion. To broaden sorghum cultivation to temperate regions, the establishment of cold-tolerant genotypes is a prioritized breeding goal. The present study aims at the quantification of seedling emergence and survival under chilling temperatures and the detection of marker-trait associations controlling temperature-related seedling establishment. A diversity set consisting of 194 biomass sorghum lines was subjected to extensive phenotyping comprising field trials and controlled environment experiments. The final emergence percentage (FEP) under field conditions was significantly reduced under cold stress. Broad-sense heritability was h 2 = 0.87 for FEP in the field and h 2 = 0.93 for seedling survival rate (SR) under controlled conditions. Correlations between FEP in the field and under controlled conditions were low; higher correlations were observed between field FEP and SR in controlled environments. Genome-wide association studies (GWAS) were conducted using 44,515 single nucleotide polymorphisms (SNPs) and revealed eight regions with suggestive marker-trait associations for FEP and SR on chromosomes SBI-01, -02, -03, -06, -09, and -10 (p < 5.7 × 10-5) and a significant association on SBI-06 for field FEP (p < 2.9 × 10-6). Although not significant under controlled conditions, SR of genotypes carrying the minor allele on the field FEP quantitative trait loci (QTL) on SBI-06 was on average 13.1% higher, while FEP under controlled conditions was on average 9.7% higher with a linearly decreasing effect with increasing temperatures (R 2 = 0.82). Promising candidate genes putatively conferring seedling cold tolerance were identified.

Unravelling the genetic complexity of sorghum seedling development under low-temperature conditions.

Sorghum is a promising alternative to maize for bioenergy production in Europe; however, its use is currently limited by poor adaptation to low temperatures during and after germination. We collected multi-trait phenotype data under optimal and suboptimal temperatures in a genetically diverse recombinant inbred line (RIL) mapping population showing contrasting segregation patterns for pre- and post-emergence chilling tolerance. Germination, emergence, seedling development, root architecture and seedling survival were assessed in two different seedlots. Emergence and root establishment were found to be the key determinants of development and survival under chilling stress. Highly interactive epistatic quantitative trait loci (QTL) hotspots, including a previously unknown QTL on Sb06 with a significant effect on prolonged chilling survival, were found to regulate different physiological mechanisms contributing to maintenance of growth and development despite the chilling temperatures. The major QTL regions harbour promising candidate genes with known roles in abiotic stress tolerance. Identification of loci in the QTL hotspot regions conferring maintenance of cell division and growth under early chilling stress represents a promising step towards breeding for successful establishment of sorghum in temperate climates.

Genetic dissection of temperature-dependent sorghum growth during juvenile development.

KEY MESSAGE: Promising genome regions for improving cold tolerance of sorghum were identified on chromosomes SBI-01, SBI-03, SBI-07, and SBI-10. Chlorophyll fluorescence had no major effect on growth rates at low temperatures. Developing fast growing sorghum seedlings is an important breeding goal for temperate climates since low springtime temperatures are resulting in a prolonged juvenile development. The adaptation of sorghum to tropical and subtropical highlands gives hint for certain genetic variation. The goals of the present study were to detect marker-trait associations for leaf and dry matter growth rate and for chlorophyll fluorescence and content (SPAD) in relation to temperature. A diversity set comprising 194 genotypes was tested in eight controlled environments with temperatures ranging from 9.4 to 20.8 °C. Significant marker-trait associations (p < 0.05) were identified for each individual temperature regime and on the parameters of regression analyses describing the responses of growth or chlorophyll related traits to temperatures. The diversity set was fingerprinted with 171 diversity array technology (DArT) and 31 simple-sequence repeat (SSR) markers. SSRs were used to analyze the population structure while association studies were performed on DArT markers. Promising marker-trait associations for growth rates in relation to temperature were detected on chromosomes SBI-01, SBI-03, SBI-07, and SBI-10. Many promising loci were also significantly associated to the results obtained in individual low-temperature environments. Marker-trait associations for chlorophyll content and fluorescence did occasionally co-locate to those for growth during juvenile development but there was no evidence supporting our hypothesis that seedling growth at low temperatures is largely influenced by SPAD or fluorescence.

A precise performance-based reimbursement model for the multi-centre NAPKON cohorts - development and evaluation.

Fair allocation of funding in multi-centre clinical studies is challenging. Models commonly used in Germany - the case fees ("fixed-rate model", FRM) and up-front staffing and consumables ("up-front allocation model", UFAM) lack transparency and fail to suitably accommodate variations in centre performance. We developed a performance-based reimbursement model (PBRM) with automated calculation of conducted activities and applied it to the cohorts of the National Pandemic Cohort Network (NAPKON) within the Network of University Medicine (NUM). The study protocol activities, which were derived from data management systems, underwent validation through standardized quality checks by multiple stakeholders. The PBRM output (first funding period) was compared among centres and cohorts, and the cost-efficiency of the models was evaluated. Cases per centre varied from one to 164. The mean case reimbursement differed among the cohorts (1173.21€ [95% CI 645.68-1700.73] to 3863.43€ [95% CI 1468.89-6257.96]) and centres and mostly fell short of the expected amount. Model comparisons revealed higher cost-efficiency of the PBRM compared to FRM and UFAM, especially for low recruitment outliers. In conclusion, we have developed a reimbursement model that is transparent, accurate, and flexible. In multi-centre collaborations where heterogeneity between centres is expected, a PBRM could be used as a model to address performance discrepancies.Trial registration: https://clinicaltrials.gov/ct2/show/NCT04768998 ; https://clinicaltrials.gov/ct2/show/NCT04747366 ; https://clinicaltrials.gov/ct2/show/NCT04679584 .

Impact of Clinical Study Implementation on Data Quality Assessments - Using Contradictions within Interdependent Health Data Items as a Pilot Indicator.

INTRODUCTION: Contradiction is a relevant data quality indicator to evaluate the plausibility of interdependent health data items. However, while contradiction assessment is achieved using domain-established contradictory dependencies, recent studies have shown the necessity for additional requirements to reach conclusive contradiction findings. For example, the oral or rectal methods used in measuring the body temperature will influence the thresholds of fever definition. The availability of this required information as explicit data items must be guaranteed during study design. In this work, we investigate the impact of activities related to study database implementation on contradiction assessment from two perspectives including: 1) additionally required metadata and 2) implementation of checks within electronic case report forms to prevent contradictory data entries. METHODS: Relevant information (timestamps, measurement methods, units, and interdependency rules) required for contradiction checks are identified. Scores are assigned to these parameters and two different studies are evaluated based on the fulfillment of the requirements by two selected interdependent data item sets. RESULTS: None of the studies have fulfilled all requirements. While timestamps and measurement units are found, missing information about measurement methods may impede conclusive contradiction assessment. Implemented checks are only found if data are directly entered. DISCUSSION: Conclusive contradiction assessment typically requires metadata in the context of captured data items. Consideration during study design and implementation of data capture systems may support better data quality in studies and could be further adopted in primary health information systems to enhance clinical anamnestic documentation.

Genetic dissection of the temperature dependent emergence processes in sorghum using a cumulative emergence model and stability parameters.

Among the major limitations for cultivating biomass sorghum in temperate regions is low temperature in spring that results in low and non-uniform emergence. The adaptation of sorghum to tropical and subtropical highlands gives hint of genetic variation in cold tolerance during emergence. The objective of the present study was to detect marker-trait associations for parameters describing the emergence process under different temperature regimes. A diversity set comprising 194 genotypes was tested in nine controlled environments with temperatures ranging from 9.4 to 19.9 °C. The genotypes were fingerprinted with 171 DArT markers. A piecewise linear regression model carried out on cumulative emergence was used to estimate genotype mean performance across environments and to carry out stability analysis on the parameters of the regression model. Base temperature (T (b)) and thermal time required for emergence (E (TS)) were determined based on median time to emergence data. Identified QTL positions were compared to marker-trait associations for final emergence percentages under low (FEP(cold)) and normal (FEP(normal)) temperatures. QTL for mean final emergence percentage (FEP), FEP(cold) and FEP(normal,) T (b) and E (TS) were detected on SBI-01. Other QTL-rich regions were located on SBI-03, SBI-04, SBI-06, SBI-08, and SBI-09. Marker-trait associations for T (b) and E (TS) co-localized to QTL for the across environment stability of FEP and the median time to emergence or emergence rate, respectively. We conclude that genome regions on six chromosomes highly influencing cold tolerance during emergence are promising for regional association studies and for the development of stable markers for marker-assisted selection.

Tick-borne encephalitis virus habitats in North East Germany: reemergence of TBEV in ticks after 15 years of inactivity.

The incidence of tick-borne encephalitis has risen in Europe since 1990 and the tick-borne encephalitis virus (TBEV) has been documented to be spreading into regions where it was not previously endemic. In Mecklenburg-West Pomerania, a federal state in Northern Germany, TBEV was not detectable in over 16,000 collected ticks between 1992 and 2004. Until 2004, the last human case of TBE in the region was reported in 1985. Following the occurrence of three autochthonous human cases of TBE after 2004, however, we collected ticks from the areas in which the infections were contracted. To increase the chance of detecting TBEV-RNA, some of the ticks were fed on mice. Using nested RT-PCR, we were able to confirm the presence of TBEV in ticks for the first time after 15 years. A phylogenetic analysis revealed a close relationship between the sequences we obtained and a TBEV sequence from Mecklenburg-East Pomerania published in 1992 and pointed to the reemergence of a natural focus of TBEV after years of low activity. Our results imply that natural foci of TBEV may either persist at low levels of activity for years or reemerge through the agency of migrating birds.

The effect of shoe lacing on plantar pressure distribution and in-shoe displacement of the foot in healthy participants.

AIMS: A proof of concept study to investigate the effect of shoe lacing on the plantar pressure distribution and in-shoe displacement of the foot during walking. METHODS: Three randomized shoe-lacing conditions, which differed in lacing tightness (comfortable, loosened, and completely loose) were investigated in 20 healthy adults. On a 10-m walking test, plantar pressures were assessed with the Pedar(®)-X in-shoe measurement system. Perceived in-shoe displacement was scored on a numerical rating scale. RESULTS: With respect to the pressure time integral statistically significant effects were found in the hallux, toes 2-5, first metatarsal head, and lateral midfoot regions. Post hoc comparison showed for the hallux: mean increase of 45.5 kPa s (95% confidence interval [CI]: 3.2-87.8 kPa s), and toes 2-5: mean increase of 23.5 kPa s (95% CI: 0.1-46.9 kPa s) between comfortably secured and completely loosened laces; lateral midfoot: mean decrease of -18.1 kPa s (95% CI: -31.5 to -4.8 kPa s) between comfortably secured and loosened laces. No significant effect was found on peak pressure, and average pressure. Participants reported a significant increase in heel slipping and in slipping back and forth of the foot as the laces were loosened. CONCLUSIONS: Looser lacing techniques resulted in small peak and average plantar pressure changes (less than 3% and 6.5% respectively). Pressure time integral under the hallux and toes 2-5 increased 16.3% and 14.5% respectively, and perceived in-shoe displacement increased as compared to comfortably secured laces. These results suggest that diabetes patients should be advised to comfortably tighten their shoelaces during the whole day.

Factors predicting the outcome of customised foot orthoses in patients with rheumatoid arthritis: a prospective cohort study.

BACKGROUND: Conservative management of foot problems in patients with rheumatoid arthritis (RA) may consist of the prescription of customised foot orthoses. Indications for foot orthoses are not clear and the effectiveness of the intervention is highly variable among patients. Knowledge on which patients benefit the most from foot orthoses can help to select patients eligible for this type of intervention. The objective of the present study was to determine clinical and demographic factors that predict the outcome of customised foot orthoses on pain and disability in patients with RA. METHODS: A total of 135 RA patients who were supplied with customised foot orthoses were included in this prospective cohort study. Pain and disability were measured before and after the intervention period using a Numeric Rating Scale (NRS) for foot pain, the Foot Function Index (FFI), the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) and a 10-meter walking test. The intervention period consisted of one or more appointments with the podiatrist during which the foot orthoses were customised.Swollen foot joint count, foot deformity scores, forefoot peak pressure, disease duration, age, gender, body mass index and baseline values of the outcome measures were selected as potential factors predicting outcome. Multivariate linear regression analyses were performed to determine factors associated with change in pain and disability (at P < 0.05). RESULTS: Disease duration was negatively associated with the change scores in NRS foot pain (P = 0.018), WOMAC pain (P = 0.001), FFI disability (P = 0.003) and WOMAC physical function (P = 0.002). Age was negatively associated with the change score in 10 meter walking time (P = 0.008). For all outcome measures baseline values were positively associated with the change scores (P < 0.001). CONCLUSIONS: Shorter disease duration predicted greater improvements in self-reported foot pain and disability, and younger age predicted greater improvements in walking time after intervention with foot orthoses. Also, higher baseline values of pain and disability predicted greater improvements. Referral for conservative management with foot orthoses in the early stage of RA seems important when aiming to achieve reduction in pain and improvement in daily activities.