Transformer-based structuring of free-text radiology report databases.

OBJECTIVES: To provide insights for on-site development of transformer-based structuring of free-text report databases by investigating different labeling and pre-training strategies. METHODS: A total of 93,368 German chest X-ray reports from 20,912 intensive care unit (ICU) patients were included. Two labeling strategies were investigated to tag six findings of the attending radiologist. First, a system based on human-defined rules was applied for annotation of all reports (termed "silver labels"). Second, 18,000 reports were manually annotated in 197 h (termed "gold labels") of which 10% were used for testing. An on-site pre-trained model (Tmlm) using masked-language modeling (MLM) was compared to a public, medically pre-trained model (Tmed). Both models were fine-tuned on silver labels only, gold labels only, and first with silver and then gold labels (hybrid training) for text classification, using varying numbers (N: 500, 1000, 2000, 3500, 7000, 14,580) of gold labels. Macro-averaged F1-scores (MAF1) in percent were calculated with 95% confidence intervals (CI). RESULTS: Tmlm,gold (95.5 [94.5-96.3]) showed significantly higher MAF1 than Tmed,silver (75.0 [73.4-76.5]) and Tmlm,silver (75.2 [73.6-76.7]), but not significantly higher MAF1 than Tmed,gold (94.7 [93.6-95.6]), Tmed,hybrid (94.9 [93.9-95.8]), and Tmlm,hybrid (95.2 [94.3-96.0]). When using 7000 or less gold-labeled reports, Tmlm,gold (N: 7000, 94.7 [93.5-95.7]) showed significantly higher MAF1 than Tmed,gold (N: 7000, 91.5 [90.0-92.8]). With at least 2000 gold-labeled reports, utilizing silver labels did not lead to significant improvement of Tmlm,hybrid (N: 2000, 91.8 [90.4-93.2]) over Tmlm,gold (N: 2000, 91.4 [89.9-92.8]). CONCLUSIONS: Custom pre-training of transformers and fine-tuning on manual annotations promises to be an efficient strategy to unlock report databases for data-driven medicine. KEY POINTS: • On-site development of natural language processing methods that retrospectively unlock free-text databases of radiology clinics for data-driven medicine is of great interest. • For clinics seeking to develop methods on-site for retrospective structuring of a report database of a certain department, it remains unclear which of previously proposed strategies for labeling reports and pre-training models is the most appropriate in context of, e.g., available annotator time. • Using a custom pre-trained transformer model, along with a little annotation effort, promises to be an efficient way to retrospectively structure radiological databases, even if not millions of reports are available for pre-training.

Reproductive decision-making by women with X-linked hypohidrotic ectodermal dysplasia.

BACKGROUND: In X-linked hypohidrotic ectodermal dysplasia (XLHED), ectodysplasin A1 (EDA1) deficiency results in malformation of hair, teeth and sweat glands. Lack of sweating which can cause life-threatening hyperthermia is amenable to intrauterine therapy with recombinant EDA1. OBJECTIVES: This study aimed at evaluating reproductive decision-making by women with XLHED and at clarifying the potential impact of a prenatal treatment option. METHODS: In a retrospective cross-sectional analysis, a 75-item questionnaire filled in by 50 women with XLHED (age 19-49 years) was assessed. RESULTS: Sixteen women (32%) prevented pregnancies because of the risk to pass on XLHED; 15 considered assisted reproduction for the same reason. Twelve women had a history of miscarriage, stillbirth or abortion, and three women reported on previous abortion of affected fetuses. When imagining to be pregnant, all except one showed interest in prenatal diagnosis of XLHED and in the possibility of treatment before birth. In 13 out of 50 women (26%), XLHED if detected prenatally would have impact on the continuation of pregnancy. Among 35 mothers of at least one affected child, XLHED had rarely been diagnosed during the first pregnancy (17%) but regularly during subsequent pregnancies (77%). Becoming aware of the condition before birth had caused a moral conflict for 50% of these women. Subjects with an affected child less frequently considered assisted reproduction to prevent XLHED (P < 0.05). In 69% of the women who reported an effect of XLHED on family planning, a prenatal treatment option for this disease would influence their decision-making. CONCLUSIONS: Many pregnant XLHED carriers who seek prenatal diagnosis experience moral conflicts. A prenatal treatment option would have strong impact on reproductive decisions, underlining the importance of adequate professional counselling.

Citrin deficiency mimicking mitochondrial depletion syndrome.

BACKGROUND: Neonatal intrahepatic cholestasis caused by citrin deficiency (CD) is a rare inborn error of metabolism due to variants in the SLC25A13 gene encoding the calcium-binding protein citrin. Citrin is an aspartate-glutamate carrier located within the inner mitochondrial membrane. CASE PRESENTATION: We report on two siblings of Romanian-Vietnamese ancestry with citrin deficiency. Patient 1 is a female who presented at age 8 weeks with cholestasis, elevated lactate levels and recurrent severe hypoglycemia. Diagnosis was made by whole exome sequencing and revealed compound heterozygosity for the frameshift variant c.852_855del, p.Met285Profs*2 and a novel deletion c.(69 + 1_70-1)_(212 + 1_231-1)del in SLC25A13. The girl responded well to dietary treatment with a lactose-free, MCT-enriched formula. Her younger brother (Patient 2) was born 1 year later and also found to be carrying the same gene variants. Dietary treatment from birth was able to completely prevent clinical manifestation until his current age of 4.5 months. CONCLUSIONS: As CD is a well-treatable disorder it should be ruled out early in the differential diagnosis of neonatal cholestasis. Due to the combination of hepatopathy, lactic acidosis and recurrent hypoglycemia the clinical presentation of CD may resemble hepatic mitochondrial depletion syndrome.

Aberrant splicing as potential modifier of the phenotype of junctional epidermolysis bullosa.

BACKGROUND: A lack or dysfunction of the anchoring protein laminin-332 in the basement membrane leads to the skin blistering disorder junctional epidermolysis bullosa (JEB). The mutation c.628G>A in the gene LAMB3 encoding the laminin ß3-chain is associated with generalized intermediate JEB; it may introduce an amino acid substitution (p.Glu210Lys) or disrupt splicing. OBJECTIVE: This retrospective study aimed at determining the effects of aberrant splicing on the JEB phenotype. METHODS: LAMB3 transcription was analysed in two siblings compound heterozygous for the LAMB3 mutations p.Glu210Lys and p.Arg635* with a diverging JEB phenotype from late childhood on. Laminin-332 levels in skin sections and in cultured keratinocytes were investigated by immunofluorescence staining. Real-time PCR was used to quantify LAMB3 expression in keratinocytes. RNA splice variants were identified by subcloning of a LAMB3 cDNA fraction and subsequent DNA sequencing. Structural models of laminin-332 helped to assess the impact of certain mutations on laminin-332 folding. RESULTS: Both siblings showed diminished LAMB3 expression. Laminin-332 was equally reduced in skin sections obtained during infancy but differed in keratinocytes isolated during adolescence. Although aberrant LAMB3 splicing with 26 variants was detected in both patients, splicing differed significantly: the full-length LAMB3 transcript harbouring the p.Glu210Lys mutation was found more often in the patient affected less severely (14/108 vs. 5/106 clones; P = 0.03). Structural modelling predicted that several deletions in LAMB3, but not the point mutation p.Glu210Lys, have an effect on laminin-332 folding and secretion. CONCLUSIONS: Differential LAMB3 mRNA splicing in the patients may explain the disparate JEB phenotype. By elucidating the regulation of laminin-332 gene expression, these findings may contribute to the development of therapeutic strategies for JEB and might help to understand phenotype modification by splice-site mutations in other hereditary diseases.

X-ray micro-computed-tomography in pediatric surgery: a new tool for studying embryos.

PURPOSE: The embryology of common congenital malformations is discussed controversially. Studies are hampered by a shortage of study material and techniques which require partial or complete preparation and therewith destruction of embryos. X-ray micro-computed-tomography (µCT) is a technical opportunity keeping the embryos intact. Thus, the aim of this study was to assess the applicability of µCT in embryonic research compared to the anatomical information obtained by scanning electron microscopy (SEM). METHODS: Chicken, rat, mouse and sheep embryos, processed either for SEM studies or as whole embryos, were imaged in three-dimensional (3D) using µCT. The obtained two-dimensional (2D) digital datasets were volume rendered by tomographic reconstruction software and studied using analysis software. RESULTS: All embryos were µCT scanned without technical problems. The quality of the µCT images (image contrast, anatomical details) was excellent, but varied depending on age and species studied. µCT imaging allowed a more comprehensive anatomical/morphological analysis but showed less surface details compared to SEM. CONCLUSION: µCT is a technique suitable and innovative for pediatric surgical research, which allows detailed evaluation of entire embryos without time- and specimen-consuming micro-dissection. Samples prepared for SEM can be used for µCT and vice versa.

Doubly Dressed Bosons: Exciton Polaritons in a Strong Terahertz Field.

We demonstrate the existence of a novel quasiparticle, an exciton in a semiconductor doubly dressed with two photons of different wavelengths: a near infrared cavity photon and terahertz (THz) photon, with the THz coupling strength approaching the ultrastrong coupling regime. This quasiparticle is composed of three different bosons, being a mixture of a matter-light quasiparticle. Our observations are confirmed by a detailed theoretical analysis, treating quantum mechanically all three bosonic fields. The doubly dressed quasiparticles retain the bosonic nature of their constituents, but their internal quantum structure strongly depends on the intensity of the applied terahertz field.

Transcranial direct current stimulation (tDCS) to the supplementary motor area (SMA) influences performance on motor tasks.

The supplementary motor area (SMA) is believed to be highly involved in the planning and execution of both simple and complex motor tasks. This study aimed to examine the role of the SMA in planning the movements required to complete reaction time, balance, and pegboard tasks using anodal transcranial direct current stimulation (tDCS), which passes a weak electrical current between two electrodes, in order to modulate neuronal activity. Twenty healthy adults were counterbalanced to receive either tDCS (experimental condition) or no tDCS (control condition) for 3 days. During administration of tDCS, participants performed a balance task significantly faster than controls. After tDCS, subjects significantly improved their simple and choice reaction time. These results demonstrate that the SMA is highly involved in planning and executing fine and gross motor skill tasks and that tDCS is an effective modality for increasing SMA-related performance on these tasks. The findings may be generalizable and therefore indicate implications for future interventions using tDCS as a therapeutic tool.

Outcome, comorbidity, hospitalization and 30-day mortality after closure of acute perforations and postoperative anastomotic leaks by the over-the-scope clip (OTSC) in an unselected cohort of patients.

BACKGROUND: Acute gastrointestinal (GI) wall defects contain a high risk of morbidity and mortality and may be closed endoscopically by a full-thickness over-the-scope clip (OTSC). METHODS: Unselected consecutive patients presenting with acute non-surgical perforations or postoperative anastomotic leaks or perforations underwent attempted OTSC placement as primary closure method after interdisciplinary consensus in three tertiary referral centres. Their clinical data and intervention characteristics were evaluated in an intention to treat analysis during a 24-month period to assess closure rates, 30-day mortality, hospitalization and comorbidity. RESULTS: In total, 34 patients (16 females, 18 males, 69.5 years) were included with 22 non-surgical perforations and 12 postoperative anastomotic leaks or perforations. Definitive closure of the perforations and leaks was achieved in 26/34 patients (76.5 %). Successful closure of the GI wall defect resulted in a significantly shorter hospital stay (8 days, p = 0.03) and was significantly correlated with comorbidity (r = 0.56, p = 0.005). In the group with OTSC failure, hospitalization was 18 days and 6 of 8 patients (75 %) required immediate surgery. Three deaths occurred in the group with successful OTSC closure due to comorbidity, while one death in the OTSC failure group was related to a refractory perforation. Favourable indications and locations for a successful OTSC procedure were identified as PEG complications, endoscopic or postoperative leaks of stomach, colon or rectum, respectively. CONCLUSIONS: In unselected patients, OTSC was effective for closure of acute GI wall defects in more than 75 % of all patients. Clinical success and short hospitalization were best achieved in patients without comorbidity, but closure of the perforation or the anastomotic leak was found to be not the only parameter relevant for patient outcome and mortality.

Quality of life in climacteric women.

Health-related quality of life (HRQoL) refers to the effects of an individual's physical state on all aspects of psychosocial functioning. For postmenopausal women, HRQoL is the only global criterion that is decisive for their daily well-being. Symptoms experienced during menopause and sociodemographic characteristics affect quality of life in postmenopausal women. In younger, symptomatic, postmenopausal women, HRQoL may be significantly diminished. However, quality of life after menopause is influenced by many additional, non-menopausal factors. In the last decades, more specific symptom lists or other questionnaires have been developed. Such scales would qualify as standardized or disease-specific by fulfilling four criteria: (1) they have been constructed on the basis of a factor analysis; (2) they consist of several subscales, each measuring a different aspect of a specific symptomatology; (3) the scales possess sound psychometric properties; and (4) they have been standardized using adequate populations of women. A variety of instruments currently dominating international practice are here reviewed. Therapeutic approaches that treat climacteric symptoms and all measures ameliorating unfavorable non-hormonal factors could improve HRQoL among postmenopausal women. This includes partnership and sexual counseling as well as psychosocial measures. Menopausal hormone therapy (MHT) may reverse this deterioration of HRQoL if it is due to postmenopausal estrogen deficiency. On the contrary, when MHT is prescribed to asymptomatic younger and older postmenopausal women, no gain in HRQoL can be obtained.

[Syncope, falls and vertigo]. / Synkope, Sturz, Schwindel.

Dizziness/vertigo, falls and syncope are among the most common reasons for seeking medical care. As clinical entities they share common pathogenetic and clinical features and differences. The diagnostic work-up can often be initiated in a general practitioner's or internist's practice and, if necessary, completed in an interdisciplinary emergency unit. Simple diagnostic tools can be used in an outpatient setting to obtain valuable diagnostic information. First and foremost, it is important to differentiate between prognostically favorable clinical events and potentially serious disease. In younger patients diagnostic procedures should primarily focus on potential structural cardiac disease and/or primary arrhythmia. The same applies to elderly patients in whom, however, multicausal clinical symptoms and severe complications in the case of falls are characteristic. Elderly patients frequently require the involvement of various clinical specialties to investigate a broad spectrum of potential differential diagnoses in an interdisciplinary diagnostic approach, which is not always available in practice. In the emergency unit, decisions regarding inpatient care need to be made individually. In elderly patients, inpatient care is sometimes necessary not only due to acute disease, but also in order to ensure social care. Geriatric day hospitals may be a suitable option for some of these patients.

Slow Noncollinear Coulomb Scattering in the Vicinity of the Dirac Point in Graphene.

The Coulomb scattering dynamics in graphene in energetic proximity to the Dirac point is investigated by polarization resolved pump-probe spectroscopy and microscopic theory. Collinear Coulomb scattering rapidly thermalizes the carrier distribution in k directions pointing radially away from the Dirac point. Our study reveals, however, that, in almost intrinsic graphene, full thermalization in all directions relying on noncollinear scattering is much slower. For low photon energies, carrier-optical-phonon processes are strongly suppressed and Coulomb mediated noncollinear scattering is remarkably slow, namely on a ps time scale. This effect is very promising for infrared and THz devices based on hot carrier effects.

The need for a holistic approach in mangrove-related fisheries research: a specific review of the German and Brazilian research project MADAM.

The main objective of the bilateral German-Brazilian mangrove development and management (MADAM) programme (mangrove dynamics and management) was to generate the scientific basis to enable the sustainable stewardship of the resources of the Caeté mangrove estuary in north-east Brazil in the sense of integrated coastal (zone) management. Main emphasis was given to fishes and crabs captured by artisanal fishermen. This paper describes the project strategy as developed and modified in the context of research results obtained over a period of 10 years. It is argued that a continuous discussion process is essential to assess the validity of the strategies formulated at the beginning of a medium-term project, particularly if the project is of an interdisciplinary nature. To achieve this, it was necessary to acquire in-depth knowledge of natural processes as well as of the relevant institutional, cultural, economic, social and political dynamics.

Noninvasive Prenatal Diagnosis of Hypohidrotic Ectodermal Dysplasia by Tooth Germ Sonography.

PURPOSE: Hypohidrotic ectodermal dysplasia, a potentially life-threatening heritable disorder, may be recognized already in utero by characteristic features such as oligodontia and mandibular hypoplasia. As therapeutic options and prognosis depend on the time point of diagnosis, early recognition was attempted during routine prenatal ultrasound examinations. SUBJECTS AND METHODS: Fetuses of nine pregnant women (one triplet and eight singleton pregnancies) with family histories of hypohidrotic ectodermal dysplasia were investigated by sonography between the 20th and 24th week of gestation. RESULTS: In 4 male and 2 female fetuses reduced amounts of tooth germs were detected, whereas 5 fetal subjects showed the normal amount. Three-dimensional ultrasound evaluation revealed mandibular hypoplasia in 5 of the 6 fetuses with oligodontia. Molecular genetic analysis and/or clinical findings after birth confirmed the prenatal sonographic diagnosis in each subject. CONCLUSION: In subjects with a family history of hypohidrotic ectodermal dysplasia, the diagnosis of this rare condition can be established noninvasively by sonography in the second trimester of pregnancy. Early recognition of the disorder may help to prevent dangerous hyperthermic episodes in infancy and may allow timely therapeutic interventions.

A mouse organotypic tissue culture model for autosomal recessive congenital ichthyosis.

BACKGROUND: Autosomal recessive congenital ichthyoses (ARCIs) are keratinization disorders caused by impaired skin barrier function. Mutations in the genes encoding the lipoxygenases 12R-LOX and eLOX-3 are the second most common cause of ARCIs. In recent years, human skin equivalents recapitulating the ARCI phenotype have been established. OBJECTIVES: To develop a murine organotypic tissue culture model for ARCI. METHODS: Epidermal keratinocytes were isolated from newborn 12R-LOX-deficient mice and cocultivated with mouse dermal fibroblasts embedded in a scaffold of native collagen type I. RESULTS: With this experimental set-up the keratinocytes formed a well-organized multilayered stratified epithelium resembling skin architecture in vivo. All epidermal layers were present and the keratinocytes within showed the characteristic morphological features. Markers for differentiation and maturation indicated regular epidermal morphogenesis. The major components of epidermal structures were expressed, and were obviously processed and assembled properly. In contrast to their wild-type counterparts, 12R-LOX-deficient skin equivalents showed abnormal vesicular structures in the upper epidermal layers correlating with altered lipid composition and increased transepidermal water loss, comparable with 12R-LOX-deficient mice. CONCLUSIONS: The mouse skin equivalents faithfully recapitulate the 12R-LOX-deficient phenotype observed in vivo, classifying them as appropriate in vitro models to study molecular mechanisms involved in the development of ARCI and to evaluate novel therapeutic agents. In contrast to existing human three-dimensional skin models, the generation of these murine models is not constrained by a limited supply of material and does not depend on in vitro expansion and/or genetic manipulations that could result in inadvertent genotypic and phenotypic alterations.

The effect of the ANKK1/DRD2 Taq1A polymorphism on weight changes of dopaminergic treatment in prolactinomas.

Treatment with dopamine agonists in patients with prolactinomas has been associated with weight loss in short term studies. However, long-term studies on weight changes are lacking. Taq1A is a restriction fragment length polymorphism considered as a gene marker for the DRD2 gene. The presence of at least one A1 allele is linked to reduced brain dopaminergic activity due to reduced receptor binding and lower density of the dopamine 2 receptor. We aimed at testing the hypothesis that the dopaminergic treatment in prolactinoma patients leads to sustained weight loss and that the presence of diminished weight loss response under dopamine agonists is associated with the minor A1 allele of Taq1A.We included n = 44 patients (17 male and 27 female, 26 macroadenomas and 18 microadenomas) with prolactinomas treated with dopamine agonists. Outcome measures were weight and body mass index (BMI) change under dopaminergic treatment after 2 years with regard to Taq1A status and sex. We observed that the dopaminergic treatment leads to a significant mean weight loss of 3.1 ± 6.25 kg after 2 years. Regarding Taq1A polymorphisms, 21 patients were carriers of at least one A1 allele and 23 patients had a genotype of A2/A2. However, the presence of the A1 allele was neither associated with the mean BMI at baseline nor with an altered weight loss response under dopamine agonist therapy. Our results implicate that the dopaminergic treatment leads to a sustained weight loss in patients with prolactinomas after 2 years. However, there was no association to the A1 allele of Taq1A, observation that needs to be analysed in larger cohorts.

[Health risks from pest control products]. / Gesundheitliche Risiken durch Schädlingsbekämpfungsmittel.

According to European biocide legislation, pest control products require assessment and authorization by the responsible national or European authorities. Biocidal products can only be authorized if they have no unacceptable effects on human health. The health risk assessment performed for authorization comprises (a) the derivation of reference values for the active substances and substances of concern contained in the biocidal product and (b) an exposure assessment. These parameters are required for risk characterization. No unacceptable health risks are expected if the determined exposure is less than the relevant reference value. In addition, the toxicological information is used for classification of the biocidal product. The assessment may, where necessary, result in specific conditions for use or other restrictions aimed at minimizing risk. The risk to human health from pest control products is mainly based on the toxicological properties of their active substances. Commonly, the coformulants used in pest control products are of less concern than the active substances (e.g., food ingredients and animal feed products). For example, most rodenticides belong to the group of anticoagulants, which are also effective in humans. Regarding intoxications through insecticides, the group of pyrethroids is of particular importance. Fumigants containing metal phosphides, hydrogen cyanide, or sulfuryl difluoride are particularly toxic. This toxicity is linked to the high acute inhalation toxicity of the gaseous active substances themselves or, in the case of phosphides, of the released gas phosphane. The aim of health risk assessment for the authorization of biocidal products is to ensure their safe application for users and all other persons involved, assuming an adequate and label-compliant use.

["Sumo-compression" Stops Post PartumHaemorrhage].

Post partum haemorrhage (PPH) from uterine atony or extensive trauma of vaginal tissue is a major cause of maternal mortality. Compression of vaginal tissue and uterus by tightly packing the vagina with laparotomy pads is described as a novel approach for the management of PPH. A bandage is placed as a very tight belt above the uterus. Counterpressure is achieved by a second bandage, which runs from anterior to posterior and is tied to the belt pressing the pads inside the vagina firmly against the uterus. The term "Sumo-compression" was chosen to remind people of the pants of the Japanese wrestlers. Using this method 5 women were successfully treated between January 2010 and October 2012.

Feedback effect during ultrafast demagnetization dynamics in ferromagnets.

Motivated by the recent controversy about the importance of spin-flip scattering for ultrafast demagnetization in ferromagnets, we study the spin-dependent electron dynamics based on a dynamical Elliott-Yafet mechanism. The key improvement to earlier approaches is the use of a modified Stoner model with a dynamic exchange splitting between majority and minority bands. In the framework of our microscopic model, we find a novel feedback effect between the time-dependent exchange splitting and the spin-flip scattering. This feedback effect allows us to reproduce important properties of the demagnetization dynamics quantitatively. Our results demonstrate that in general Elliott-Yafet spin-flip scattering needs to be taken into account to obtain a microscopic picture of demagnetization dynamics.

Observation of forbidden exciton transitions mediated by Coulomb interactions in photoexcited semiconductor quantum wells.

We use terahertz pulses to induce resonant transitions between the eigenstates of optically generated exciton populations in a high-quality semiconductor quantum well sample. Monitoring the excitonic photoluminescence, we observe transient quenching of the 1s exciton emission, which we attribute to the terahertz-induced 1s-to-2p excitation. Simultaneously, a pronounced enhancement of the 2s exciton emission is observed, despite the 1s-to-2s transition being dipole forbidden. A microscopic many-body theory explains the experimental observations as a Coulomb-scattering mixing of the 2s and 2p states, yielding an effective terahertz transition between the 1s and 2s populations.