bluuebunny/crossref_metadata_2025 huggingface dataset:
Remarkably LowKIRandHLADiversity in Amerindians Reveals Signatures of Strong Purifying Selection Shaping the CentromericKIRRegion
Authors: de Brito Vargas Luciana , Beltrame Marcia H , Ho Brenda , Marin Wesley M , Dandekar Ravi , Montero-Martín Gonzalo , Fernández-Viña Marcelo A , Hurtado A Magdalena , Hill Kim R , Tsuneto Luiza T , Hutz Mara H , Salzano Francisco M , Petzl-Erler Maria Luiza , Hollenbach Jill A , Augusto Danillo G
Published: October 2021

The killer-cell immunoglobulin-like receptors (KIR) recognize human leukocyte antigen (HLA) molecules to regulate the cytotoxic and inflammatory responses of natural killer cells. KIR genes are encoded by a rapidly evolving gene family on chromosome 19 and present an unusual variation of presence and absence of genes and high allelic diversity. Although many studies have associated KIR polymorphism with susceptibility to several diseases over the last decades, the high-resolution allele-level haplotypes have only recently started to be described in populations. Here, we use a highly innovative custom next-generation sequencing method that provides a state-of-art characterization of KIR and HLA diversity in 706 individuals from eight unique South American populations: five Amerindian populations from Brazil (three Guarani and two Kaingang); one Amerindian population from Paraguay (Aché); and two urban populations from Southern Brazil (European and Japanese descendants from Curitiba). For the first time, we describe complete high-resolution KIR haplotypes in South American populations, exploring copy number, linkage disequilibrium, and KIR–HLA interactions. We show that all Amerindians analyzed to date exhibit the lowest numbers of KIR–HLA interactions among all described worldwide populations, and that 83–97% of their KIR–HLA interactions rely on a few HLA-C molecules. Using multiple approaches, we found signatures of strong purifying selection on the KIR centromeric region, which codes for the strongest NK cell educator receptors, possibly driven by the limited HLA diversity in these populations. Our study expands the current knowledge of KIR genetic diversity in populations to understand KIR–HLA coevolution and its impact on human health and survival.
HI-NESS: a family of genetically encoded DNA labels based on a bacterial nucleoid-associated protein
Authors: Rashid Fatema-Zahra M , Mahlandt Eike , van der Vaart Michiel , Boer Daphne E C , Varela Alvarez Monica , Henneman Bram , Brocken Daan J W , Voskamp Patrick , Blok Anneloes J , Shimizu Thomas S , Meijer Annemarie H , Luijsterburg Martijn S , Goedhart Joachim , Crémazy Frédéric G E , Dame Remus T
Published: October 2021

The interplay between three-dimensional chromosome organisation and genomic processes such as replication and transcription necessitates in vivo studies of chromosome dynamics. Fluorescent organic dyes are often used for chromosome labelling in vivo. The mode of binding of these dyes to DNA cause its distortion, elongation, and partial unwinding. The structural changes induce DNA damage and interfere with the binding dynamics of chromatin-associated proteins, consequently perturbing gene expression, genome replication, and cell cycle progression. We have developed a minimally-perturbing, genetically encoded fluorescent DNA label consisting of a (photo-switchable) fluorescent protein fused to the DNA-binding domain of H-NS — a bacterial nucleoid-associated protein. We show that this DNA label, abbreviated as HI-NESS (H-NS-based indicator for nucleic acid stainings), is minimally-perturbing to genomic processes and labels chromosomes in eukaryotic cells in culture, and in zebrafish embryos with preferential binding to AT-rich chromatin.
Mental health care utilization by first responders after Paris attacks
Authors: Motreff Y , Pirard P , Vuillermoz C , Rabet G , Petitclerc M , Stene L Eilin , Baubet T , Chauvin P , Vandentorren S
Published: October 2021

Background

First responders (FRs) are frequently exposed to potentially traumatic events, including terror attacks, and may consequently be at risk of developing mental health disorders. Prior research suggests that FRs with mental health disorders often do not receive appropriate treatment. More knowledge is needed about their use of mental health care (MHC).

Aims

This study aimed to identify factors associated with receiving immediate support, post-immediate support and engagement in MHC among FRs of the November 2015 terror attacks in Paris.

Methods

A web-based study was conducted 8–12 months after the attacks on 663 FRs who were mobilized during the night and/or the aftermath of the attacks. Logistic regression was performed to analyse factors associated with MHC.

Results

Overall, 44 FRs sought MHC. Among FRs with post-traumatic stress disorder (PTSD), partial PTSD or depression (n = 60), 38% sought MHC (n = 23). Post-immediate support was associated with immediate support, and both were associated with knowing someone who could help regarding the potential psychological risks following a traumatic event. MHC engagement was associated with a history of MHC, post-immediate support and the presence of PTSD, partial PTSD or depression.

Conclusions

Among FRs with PTSD, partial PTSD or depression, few sought MHC. Improved access to MHC for FRs after terror attacks is essential. Knowing someone who could help regarding potential psychological risks may facilitate immediate and/or post-immediate support. Furthermore, post-immediate support could encourage engagement in MHC. Efforts should be made before and after potentially traumatic events to ensure mental health education for FR.
Disentangling the stellar inclination of transiting planetary systems: Fully analytic approach to the Rossiter–McLaughlin effect incorporating the stellar differential rotation
Authors: Sasaki Shin , Suto Yasushi
Published: October 2021

The Rossiter–McLaughlin (RM) effect has been widely used to estimate the sky-projected spin-orbit angle, λ, of transiting planetary systems. Most of the previous analysis assumes that the host stars are rigid rotators in which the amplitude of the RM velocity anomaly is proportional to v⋆ sin i⋆. When their latitudinal differential rotation is taken into account, one can break the degeneracy, and determine separately the equatorial rotation velocity v⋆ and the inclination i⋆ of the host star. We derive a fully analytic approximate formula for the RM effect adopting a parametrized model for the stellar differential rotation. For those stars that exhibit a differential rotation similar to that of the Sun, the corresponding RM velocity modulation amounts to several m s−1. We conclude that the latitudinal differential rotation offers a method to estimate i⋆, and thus the full spin-orbit angle ψ, from the RM data analysis alone.
The Meanings of a Port City Boundary: Calcutta’s Maratha Ditch, c.1700–1950
Authors: Ehrlich Joshua
Published: October 2021

Global histories have fixated on connections, notably in their treatment of colonial and postcolonial port cities. While such cities have been intensely connected places, however, they have also been intensely bounded ones. The present article takes as an example of this phenomenon the archetypal port city of Calcutta (now Kolkata) and its historical boundary, the Maratha Ditch. From the eighteenth century to the twentieth century, the ditch was a vital site of meaning-making that sustained lasting political, legal and social divisions. It separated Calcutta, in an evolving fusion of concrete and abstract, formal and informal ways, from the surrounding province of Bengal and from the rest of India. Nonetheless, for generations of rulers, citizens and outside observers, refiguring or repurposing the ditch was a means to remake the city. The story told here is instructive in two broad respects. Firstly, it suggests a new way to study the history of a port city like Calcutta: from its margins. Secondly, it provides the basis for a new historical geography of the urban world: one attentive to boundaries and connections alike.
A vector system for fast-forward studies of the HOPZ-ACTIVATED RESISTANCE1 (ZAR1) resistosome in the model plant Nicotiana benthamiana
Authors: Harant Adeline , Pai Hsuan , Sakai Toshiyuki , Kamoun Sophien , Adachi Hiroaki
Published: October 2021

Nicotiana benthamiana has emerged as a complementary experimental system to Arabidopsis thaliana. It enables fast-forward in vivo analyses primarily through transient gene expression and is particularly popular in the study of plant immunity. Recently, our understanding of nucleotide-binding leucine-rich repeat (NLR) plant immune receptors has greatly advanced following the discovery of the Arabidopsis HOPZ-ACTIVATED RESISTANCE1 (ZAR1) resistosome. Here, we describe a vector system of 72 plasmids that enables functional studies of the ZAR1 resistosome in N. benthamiana. We showed that ZAR1 stands out among the coiled coil class of NLRs (CC-NLRs) for being highly conserved across distantly related dicot plant species and confirmed NbZAR1 as the N. benthamiana ortholog of Arabidopsis ZAR1. Effector-activated and autoactive NbZAR1 triggers the cell death response in N. benthamiana and this activity is dependent on a functional N-terminal α1 helix. C-terminally tagged NbZAR1 remains functional in N. benthamiana, thus enabling cell biology and biochemical studies in this plant system. We conclude that the NbZAR1 open source pZA plasmid collection forms an additional experimental system to Arabidopsis for in planta resistosome studies.
Potassium transporter TRH1/KUP4 contributes to distinct auxin-mediated root system architecture responses
Authors: Templalexis Dimitris , Tsitsekian Dikran , Liu Chen , Daras Gerasimos , Šimura Jan , Moschou Panagiotis , Ljung Karin , Hatzopoulos Polydefkis , Rigas Stamatis
Published: October 2021

In plants, auxin transport and development are tightly coupled, just as hormone and growth responses are intimately linked in multicellular systems. Here we provide insights into uncoupling this tight control by specifically targeting the expression of TINY ROOT HAIR 1 (TRH1), a member of plant high-affinity potassium (K+)/K+ uptake/K+ transporter (HAK/KUP/KT) transporters that facilitate K+ uptake by co-transporting protons, in Arabidopsis root cell files. Use of this system pinpointed specific root developmental responses to acropetal versus basipetal auxin transport. Loss of TRH1 function shows TRHs and defective root gravitropism, associated with auxin imbalance in the root apex. Cell file-specific expression of TRH1 in the central cylinder rescued trh1 root agravitropism, whereas positional TRH1 expression in peripheral cell layers, including epidermis and cortex, restored trh1 defects. Applying a system-level approach, the role of RAP2.11 and ROOT HAIR DEFECTIVE-LIKE 5 transcription factors (TFs) in root hair development was verified. Furthermore, ERF53 and WRKY51 TFs were overrepresented upon restoration of root gravitropism supporting involvement in gravitropic control. Auxin has a central role in shaping root system architecture by regulating multiple developmental processes. We reveal that TRH1 jointly modulates intracellular ionic gradients and cell-to-cell polar auxin transport to drive root epidermal cell differentiation and gravitropic response. Our results indicate the developmental importance of HAK/KUP/KT proton-coupled K+ transporters.
Asymmetric redundancy of soybean Nodule Inception (NIN) genes in root nodule symbiosis
Authors: Fu Mengdi , Sun Jiafeng , Li Xiaolin , Guan Yuefeng , Xie Fang
Published: October 2021

Nodule Inception (NIN) is one of the most important root nodule symbiotic genes as it is required for both infection and nodule organogenesis in legumes. Unlike most legumes with a sole NIN gene, there are four putative orthologous NIN genes in soybean (Glycine max). Whether and how these NIN genes contribute to soybean–rhizobia symbiotic interaction remain unknown. In this study, we found that all four GmNIN genes are induced by rhizobia and that conserved CE and CYC binding motifs in their promoter regions are required for their expression in the nodule formation process. By generation of multiplex Gmnin mutants, we found that the Gmnin1a nin2a nin2b triple mutant and Gmnin1a nin1b nin2a nin2b quadruple mutant displayed similar defects in rhizobia infection and root nodule formation, Gmnin2a nin2b produced fewer nodules but displayed a hyper infection phenotype compared to wild type (WT), while the Gmnin1a nin1b double mutant nodulated similar to WT. Overexpression of GmNIN1a, GmNIN1b, GmNIN2a, and GmNIN2b reduced nodule numbers after rhizobia inoculation, with GmNIN1b overexpression having the weakest effect. In addition, overexpression of GmNIN1a, GmNIN2a, or GmNIN2b, but not GmNIN1b, produced malformed pseudo-nodule-like structures without rhizobia inoculation. In conclusion, GmNIN1a, GmNIN2a, and GmNIN2b play functionally redundant yet complicated roles in soybean nodulation. GmNIN1b, although expressed at a comparable level with the other homologs, plays a minor role in root nodule symbiosis. Our work provides insight into the understanding of the asymmetrically redundant function of GmNIN genes in soybean.
Rhythmic Change of Cortical Hemodynamic Signals Associated with Ongoing Nociception in Awake and Anesthetized Individuals: An Exploratory Functional Near Infrared Spectroscopy Study
Authors: Peng Ke , Deepti Karunakaran Keerthana , Lee Arielle , Gomez-Morad Andrea , Labadie Robert , Mizrahi-Arnaud Arielle , Berry Delany , Kussman Barry , Zurakowski David , Micheli Lyle , Becerra Lino , Borsook David
Published: October 2021

Background

Patients undergoing surgical procedures are vulnerable to repetitive evoked or ongoing nociceptive barrage. Using functional near infrared spectroscopy, the authors aimed to evaluate the cortical hemodynamic signal power changes during ongoing nociception in healthy awake volunteers and in surgical patients under general anesthesia. The authors hypothesized that ongoing nociception to heat or surgical trauma would induce reductions in the power of cortical low-frequency hemodynamic oscillations in a similar manner as previously reported using functional magnetic resonance imaging for ongoing pain.

Methods

Cortical hemodynamic signals during noxious stimuli from the fontopolar cortex were evaluated in two groups: group 1, a healthy/conscious group (n = 15, all males) where ongoing noxious and innocuous heat stimulus was induced by a contact thermode to the dorsum of left hand; and group 2, a patient/unconscious group (n = 13, 3 males) receiving general anesthesia undergoing knee surgery. The fractional power of low-frequency hemodynamic signals was compared across stimulation conditions in the healthy awake group, and between patients who received standard anesthesia and those who received standard anesthesia with additional regional nerve block.

Results

A reduction of the total fractional power in both groups—specifically, a decrease in the slow-5 frequency band (0.01 to 0.027 Hz) of oxygenated hemoglobin concentration changes over the frontopolar cortex—was observed during ongoing noxious stimuli in the healthy awake group (paired t test, P = 0.017; effect size, 0.70), and during invasive procedures in the surgery group (paired t test, P = 0.003; effect size, 2.16). The reduction was partially reversed in patients who received a regional nerve block that likely diminished afferent nociceptive activity (two-sample t test, P = 0.002; effect size, 2.34).

Conclusions

These results suggest common power changes in slow-wave cortical hemodynamic oscillations during ongoing nociceptive processing in conscious and unconscious states. The observed signal may potentially promote future development of a surrogate signal to assess ongoing nociception under general anesthesia.

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What We Already Know about This Topic

What This Article Tells Us That Is New
Use of Immediate Postpartum Long-Acting Reversible Contraception Before and After a State Policy Mandated Inpatient Access
Authors: Brant Ashley R. , Kollikonda Swapna , Yao Meng , Mei Lin , Emery Jonathan
Published: October 2021

OBJECTIVE:

To assess the rate of immediate postpartum long-acting reversible contraceptive (LARC) use in a multihospital health care system 2 years before and after the policy was implemented, and to assess factors associated with LARC use and repeat pregnancy rates within 12 months after delivery.

METHODS:

We conducted a retrospective chart review of all patients giving birth at three Cleveland Clinic Ohio hospitals from July 1, 2015, to June 30, 2019. We reviewed the inpatient medication reconciliation to identify the LARC initiation rate. We compared all patients who received inpatient postpartum LARC to a 1:3 matched sample of patients who did not receive LARC, matched by delivery date and location, to identify patient characteristics associated with LARC use. The electronic medical record (Epic) was reviewed to identify new pregnancies occurring within 12 months postdelivery.

RESULTS:

We identified 17,848 deliveries prepolicy and 18,555 deliveries postpolicy. Immediate postpartum LARC was used by 0.5% (monthly range 0–2.1%) of patients prepolicy and 11.6% (monthly range 8.3–15.4%) of patients postpolicy. Levonorgestrel intrauterine devices (IUDs) were used by 56.5%, implants by 29.1%, and copper IUDs by 14.5% of LARC users. Characteristics associated with LARC use included younger age, public insurance, non-White race, Hispanic or Latina ethnicity, higher body mass index, sexually transmitted infection in pregnancy, and tobacco use. Long-acting reversible contraceptive users had a lower rate of repeat pregnancy at 12 months postpartum compared with the non-LARC group (1.9% vs 3.6%, P<.001).

CONCLUSION:

Immediate postpartum LARC use increased after a state policy change mandated universal access and was associated with decreased pregnancy rates in the first year postdelivery.
Association of Epilepsy and Severe Maternal Morbidity
Authors: Panelli Danielle M. , Leonard Stephanie A. , Kan Peiyi , Meador Kimford J. , McElrath Thomas F. , Darmawan Kelly F. , Carmichael Suzan L. , Lyell Deirdre J. , El-Sayed Yasser Y. , Druzin Maurice L. , Herrero Tiffany C.
Published: October 2021

OBJECTIVE:

To evaluate severe maternal morbidity (SMM) among patients with epilepsy and patients without epilepsy.

METHODS:

We retrospectively examined SMM using linked birth certificate and maternal hospital discharge records in California between 2007 and 2012. Epilepsy present at delivery admission was the exposure and was subtyped into generalized, focal and other less specified, or unspecified. The outcomes were SMM and nontransfusion SMM from delivery up to 42 days’ postpartum, identified using Centers for Disease Control and Prevention indicators. Multivariable logistic regression models were used to adjust for confounders, which were selected a priori. We also estimated the association between epilepsy and SMM independent of comorbidities by using a validated obstetric comorbidity score. Severe maternal morbidity indicators were then compared using the same multivariable logistic regression models.

RESULTS:

Of 2,668,442 births, 8,145 (0.3%) were to patients with epilepsy; 637 (7.8%) had generalized, 6,250 (76.7%) had focal or other less specified, and 1,258 (15.4%) had unspecified subtypes. Compared with patients without epilepsy, patients with epilepsy had greater odds of SMM (4.3% vs 1.4%, adjusted odds ratio [aOR] 2.91, 95% CI 2.61–3.24) and nontransfusion SMM (2.9% vs 0.7%, aOR 4.16, 95% CI 3.65–4.75). Epilepsy remained significantly associated with increased SMM and nontransfusion SMM after additional adjustment for the obstetric comorbidity score, though the effects were attenuated. When grouped by organ system, all SMM indicators were significantly more common among patients with epilepsy—most notably those related to hemorrhage and transfusion.

CONCLUSION:

Severe maternal morbidity was significantly increased in patients with epilepsy, and SMM indicators across all organ systems contributed to this.
Homicide During Pregnancy and the Postpartum Period in the United States, 2018–2019
Authors: Wallace Maeve , Gillispie-Bell Veronica , Cruz Kiara , Davis Kelly , Vilda Dovile
Published: October 2021

OBJECTIVE:

To estimate the national pregnancy-associated homicide mortality ratio, characterize pregnancy-associated homicide victims, and compare the risk of homicide in the perinatal period (pregnancy and up to 1 year postpartum) with risk among nonpregnant, nonpostpartum females aged 10–44 years.

METHODS:

Data from the National Center for Health Statistics 2018 and 2019 mortality files were used to identify all female decedents aged 10–44 in the United States. These data were used to estimate 2-year pregnancy-associated homicide mortality ratios (deaths/100,000 live births) for comparison with homicide mortality among nonpregnant, nonpostpartum females (deaths/100,000 population) and to mortality ratios for direct maternal causes of death. We compared characteristics and estimated homicide mortality rate ratios and 95% CIs between pregnant or postpartum and nonpregnant, nonpostpartum victims for the total population and with stratification by race and ethnicity and age.

RESULTS:

There were 3.62 homicides per 100,000 live births among females who were pregnant or within 1 year postpartum, 16% higher than homicide prevalence among nonpregnant and nonpostpartum females of reproductive age (3.12 deaths/100,000 population, P<.05). Homicide during pregnancy or within 42 days of the end of pregnancy exceeded all the leading causes of maternal mortality by more than twofold. Pregnancy was associated with a significantly elevated homicide risk in the Black population and among girls and younger women (age 10–24 years) across racial and ethnic subgroups.

CONCLUSION:

Homicide is a leading cause of death during pregnancy and the postpartum period in the United States. Pregnancy and the postpartum period are times of elevated risk for homicide among all females of reproductive age.
Complete Response to Combination Nivolumab and Ipilimumab in Recurrent Neuroendocrine Carcinoma of the Cervix
Authors: Paterniti Thomas A. , Dorr Katie , Ullah Asad , White Joseph , Williams Hadyn , Ghamande Sharad
Published: October 2021

BACKGROUND:

Small cell neuroendocrine carcinoma of the cervix is a rare, aggressive tumor treated with a combination of surgery, chemotherapy, and radiation. Survival rates are poor, and innovative therapies are needed.

CASE:

A 52-year-old woman was diagnosed with small cell neuroendocrine carcinoma of the cervix. Over a 10-year period, she was treated with six different systemic therapeutic regimens, underwent planned hysterectomy with bilateral salpingo-oophorectomy, and received radiation to the pelvis and brain. After a second recurrence of disease, she was treated with a combination of nivolumab and ipilimumab and experienced a complete and durable response.

CONCLUSION:

The combination of nivolumab and ipilimumab may represent a promising new treatment option for recurrent small cell neuroendocrine carcinoma of the cervix.
Pregnant Individuals' Views on Fetal Tissue Research in the United States
Authors: Spach Natalie C. , Jaffe Elana F. , Sullivan Kristen A. , Goldfarb Ilona T. , Anderson Jean R. , Coleman Jenell , Gilbert Sappho Z. , Gross Marielle S. , Rahangdale Lisa , Faden Ruth R. , Lyerly Anne D.
Published: October 2021

OBJECTIVE:

Fetal tissue research has driven significant medical advances but remains publicly contentious in the United States. The views of pregnant individuals in the United States regarding the donation of fetal tissue offer an important and previously unexplored perspective on this issue.

METHODS:

We conducted a secondary analysis of data from two separate, broader qualitative studies. Pregnant and recently pregnant individuals (N=79) from clinical sites at the University of North Carolina at Chapel Hill, Johns Hopkins University, and Massachusetts General Hospital were interviewed individually using a semi-structured guide addressing a range of issues related to infectious disease research and pregnancy, including the acceptability of fetal tissue research. Interviews were transcribed, coded, and analyzed for emergent themes.

RESULTS:

Among this sample of predominantly Black (61%), reproductive-aged pregnant and recently pregnant participants, the majority (72%) generally supported fetal tissue research. The following three themes were identified: choice, respect, and meaning. Respondents discussed the deeply personal nature of decisions surrounding fetal tissue research, emphasizing the importance of informed consent and respect for the person's emotional state when approaching for consent. The ways in which participants regarded how to respectfully handle fetal tissue also shaped views about the acceptability of donation, both for and against. For many participants, fetal tissue donation to research represented one way of ascribing meaning to pregnancy termination or loss.

CONCLUSION:

Among this diverse sample of pregnant and recently pregnant individuals, most were supportive of fetal tissue donation for research. A better understanding of pregnant individuals' views on this topic may lead to policies and practices that are congruent with the needs and values of people facing decisions regarding the disposition of fetal remains.
Trends in the Use of Minimally Invasive Adnexal Surgery in the United States
Authors: Dioun Shayan , Huang Yongmei , Melamed Alexander , Gockley Allison , St. Clair Caryn M. , Hou June Y. , Tergas Ana I. , Khoury-Collado Fady , Hershman Dawn L. , Wright Jason D.
Published: October 2021

OBJECTIVE:

To examine the utilization of minimally invasive adnexal surgery, including ovarian cystectomy and oophorectomy, among women with benign gynecologic diseases and compare the associated morbidity and mortality of minimally invasive and open surgery.

METHODS:

Women with benign ovarian pathology who underwent an ovarian cystectomy or oophorectomy from 2016 through 2018 in the Nationwide Ambulatory Surgery Sample and Nationwide Inpatient Sample databases were included. Patients with a diagnosis of gynecologic malignancy or concurrent hysterectomy were excluded. Population-level weighted estimates were developed, and perioperative morbidity, mortality, and hospital charges were examined based on surgical approach for each procedure.

RESULTS:

The cohort included 351,207 women who underwent oophorectomy and 220,893 women who underwent cystectomy, when weighted representing 547,836 and 328,408 patients, respectively, nationwide. A minimally invasive surgical approach was used in 294,190 (89.6%) patients who underwent ovarian cystectomy, and in 478,402 (87.3%) of patients who underwent oophorectomy. Use of minimally invasive surgery for cystectomy increased from 88.7% in 2016 to 91.0% in 2018, and the rate of minimally invasive surgery for oophorectomy increased from 85.8% to 88.7% over the same time period (P<.001 for both). The complication rates for ovarian cystectomy were 2.7% for minimally invasive surgery and 8.8% for laparotomy (P<.001); for oophorectomy the complication rate was 3.1% for minimally invasive surgery and 22.9% for laparotomy (P<.001).

CONCLUSION:

Minimally invasive surgery is used in the majority of women who are undergoing oophorectomy and ovarian cystectomy for benign indications. Compared with laparotomy, minimally invasive surgery is associated with fewer complications.
Vocal Turn-Taking in Families With Children With and Without Hearing Loss
Authors: Kondaurova Maria V. , Zheng Qi , VanDam Mark , Kinney Kaelin
Published: October 2021

Objective:

Vocal turn-taking is an important predictor of language development in children with and without hearing loss. Most studies have examined vocal turn-taking in mother-child dyads without considering the multitalker context in a child’s life. The present study investigates the quantity of vocal turns between deaf and hard-of-hearing children and multiple members of their social environment.

Design:

Participants were 52 families with children who used hearing aids (HA, mean age 26.3 mo) or cochlear implants (CI, mean age 63.2 mo) and 27 families with normal-hearing (NH, mean age 26.6 mo) children. The Language ENvironment Analysis system estimated the number of conversational turns per hour (CTC/hr) between all family members (i.e., adult female, adult male, target child, and other child) during full-day recordings over a period of about 1 year.

Results:

The CTC/hr was lower between the target child and the adult female or adult male in the CI compared with the HA and NH groups. Initially, CTC/hr was higher between the target child and the adult female than between the adult male or the other child. As the child’s age increased, turn-taking between the target child and the adult female increased in comparison to that between the target child and the adult male. Over time, turn-taking between the target child and the other child increased and exceeded turn-taking between the target child and the adult caregivers. The increase was observed earlier in families with siblings compared with those without.

Conclusions:

The quantity of vocal turn-taking depends on the degree of child hearing loss and the relationship between the children and the members of their social environment. Longitudinally, the positive effect of an assistive device on the quantity of turns between the children and their family members was found. The effect was stronger in families with siblings.
Impact of Intraoperative Hypothermia on Transfusion Requirements in Patients With Pelvic and Acetabular Trauma
Authors: Goel Rahul , Boissonneault Adam , Grissom Helyn , Arora Sona , Hernandez-Irizarry Roberto , Schenker Mara , Maceroli Michael
Published: October 2021

Objectives:

To explore the association between intraoperative hypothermia and perioperative blood loss and blood transfusion requirements in patients with operative pelvic and acetabular fractures.

Design:

Retrospective review.

Setting:

Single, Level 1 trauma center in Atlanta, Georgia.

Patients/Participants:

Three hundred seventy-four patients who underwent surgical fixation of an acetabular fracture and/or pelvic ring injury at a single Level 1 trauma center during the years 2013–2017.

Main Outcome Measures:

Estimated blood loss during surgery (EBL, mL), drain output (mL) on postoperative day 1 (POD1), and rate of postoperative packed red blood cell (pRBC) transfusion (%).

Results:

A significant association was found between intraoperative hypothermia and postoperative transfusion requirement (P = 0.016). The rate of postoperative blood transfusion was 42% for patients with intraoperative hypothermia compared with 28% for controls. In a subgroup analysis of patients presenting with an admission acidosis, the rate of postoperative transfusion was significantly increased to more than 4 times as likely when intraoperative hypothermia was present, even after controlling for admission hemoglobin, Injury Severity Score, and rate of preoperative transfusion (OR 4.4; P = 0.018).

Conclusions:

For patients with pelvic trauma who present with an admission acidosis, intraoperative hypothermia is an independent risk factor for postoperative blood transfusion. This information is clinically important given the modifiable nature of intraoperative patient temperature and the known complications and sequelae associated with increased transfusion rates.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Zero Patient-controlled Analgesia is an Achievable Target for Postoperative Rapid Recovery Management of Adolescent Idiopathic Scoliosis Patients
Authors: Sarwahi Vishal , Hasan Sayyida , Liao Benita , Galina Jesse , Atlas Aaron , Lo Yungtai , Lee Andrew , Lentz Jonathon , Amaral Terry , Kars Michelle
Published: October 2021

Study Design.

Retrospective review.

Objective.

The objective of this study was to report on one institution's use of single bolus micro-dose intrathecal morphine as part of a rapid recovery pathway during posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) and its comparison to patients whose pain was controlled with patient-controlled analgesia (PCA).

Summary of Background Data.

Narcotic substance addiction has risen across all patient populations, including pediatrics. Narcotics have been historically used in complex spine surgeries as a measure of pain control, predominantly provided as PCA and additional take-home medication.

Methods.

AIS patients undergoing PSF from 2015 to 2019 were reviewed. In 2018, we instituted a standardized rapid recovery pathway for scoliosis patients undergoing PSF utilizing micro-dose intrathecal morphine (ITM-RRP). Before this, traditional protocol with PCA was used for postoperative management. Perioperative data, morphine consumption and prescription refill requests were compared.

Results.

There were 373 AIS patients total in this study, of which 250 patients were in the PCA group and 123 in the ITM-RRP Group. Preoperative Cobb angles (P = 0.195), as well as levels fused (P = 0.481) and body mass index (P = 0.075) were similar. 69.4% of ITM-RRP patients had a length of stay ≤3 days, significantly >11.6% of PCA patients (P < 0.001). ITM-RRP patients began ambulating significantly earlier with 84.6% patients out of bed by postoperative day 1 versus 8% PCA patients (P < 0.001). Additionally, ITM-RRP patients had significantly lower VAS pain scores with activity and earlier initial bowel movements (P < 0.001).

Postoperative emesis was similar (P = 0.11). No patients had pruritus, respiratory depression, or required supplemental oxygenation.

Conclusion.

This is the first study to show that a rapid recovery protocol utilizing single micro-dose ITM with oral analgesics have adequate recovery, significantly better postoperative pain control and superior perioperative outcomes to traditional protocols using PCA in the AIS population following PSF.

Level of Evidence: 3
Implant Microbial Colonization Detected by Sonication as a Cause for Spinal Device Failure
Authors: García-Pérez Daniel , Lagares Alfonso , Castaño-León Ana María , Panero Irene , Munarriz Pablo M. , Delgado-Fernández Juan , Jiménez-Roldán Luis , Pérez-Núñez Angel , Alén Jose Antonio F. , Paredes Igor
Published: October 2021

Study Design.

A prospective single center observational study.

Objectives.

The aim of this study was to examine the potential role of sonication in the diagnosis of low-grade infections and its association with pedicle screw (PS) loosening, and to describe risk factors and radiological findings associated with spinal implant infection.

Summary of Background Data.

Although PS loosening has mainly been attributed to mechanical overload, implant colonization and biofilm formation have recently been suggested. Culturing of sonication fluid implants is promising in the field of spine instrumentation infection, but little data are available.

Methods.

We prospectively included all patients who were subjected to implant removal. PS loosening was assessed with computed tomography (CT) scan. Different clinical and radiological parameters which could serve as indicators of implant infection were studied.

Results.

Thirty-eight patients were included in the study and 11 of them (29%) had a positive sonication result. Patients with spinal implant infection were associated with screw loosening (P = 0.005). Particularly, those screws with a positive microbiological culture showed signs of screw loosening in the preoperative CT scan (P < 0.001). Our results also showed that radiological screw loosening at L1-L3 level, and loosened larger constructs were associated with screw microbial colonization. The most common isolated microorganisms were coagulase-negative staphylococci and Cutibacterium acnes. An implant-based multivariate analysis indicated that screw loosening, the absence of prophylactic cefazolin, ICU hospitalization, screw breakage, and L1-L3 spine level were independent risk factors for implant-associated infection. Our model exhibited a high predictive power with an area under the curve of 0.937.

Conclusion.

As clinical presentation of deep implant chronic infection is unspecific, consideration of these factors enables preoperative prediction and risk stratification of implant colonization, thus helping patient's management.

Level of Evidence: 3
Atlantoaxial Non-Fusion Using Biomimetic Artificial Atlanto-Odontoid Joint
Authors: Zang Quanjin , Li Jiaxi , Liu Yanming , Li Haopeng , Cao Kai , Guo Shuai , Li Ke , Sun Lei , He Xijing
Published: October 2021

Study Design.

A biomechanical in vitro investigation.

Objective.

To evaluate the function and stability of self-designed biomimetic artificial atlanto-odontoid joint (BAAOJ) replacement on the atlantoaxial joint.

Summary of Background Data.

Upper cervical fusion surgery is a common treatment for various atlantoaxial disorders, and favorable clinical outcome has been achieved. However, the fusion surgery results in loss of atlantoaxial motion as well as adjacent segments degeneration, reducing the quality of life of patients and might produce severe neurological symptoms. Non-fusion technology is expected to solve the above problems, but various designed devices have certain defects and are still in the exploratory phase.

Materials and Methods.

Biomechanical tests were conducted on 10 fresh human cadaveric craniocervical specimens in the following sequence: 1) intact condition, 2) after the BAAOJ arthroplasty, 3) after BAAOJ fatigue test, 4) after odontoidect-omy, and 5) after anterior rigid plate fixation. Three-dimensional movements of the C1-C2 segment were evaluated to investigate the function and stability of BAAOJ arthroplasty compared with the intact condition after the BAAOJ fatigue test, odontoidect-omy, and rigid plate fixation.

Results.

Comparing the BAAOJ implantation to the intact state, the range of motion and neutral zone were slightly reduced in all directions (P > 0.05). Compared with the rigid plate fixation, the BAAOJ implantation significantly increased the range of motion and neutral zone in all directions, especially in the axial rotation (P < 0.05).

Conclusion.

We designed a BAAOJ for correcting atlantoaxial disorders arising from atlantoaxial instability. As a non-fusion device, the most critical feature of BAAOJ replacement is the retention of flexion-extension, lateral bending, and axial rotation range of motion similar to the normal state. It can also stabilize the atlantoaxial complex, and the BAAOJ itself has a good initial stability.

Level of Evidence: 4
Facet Joint Opening on Computed Tomography Is a Predictor of Poor Clinical Outcomes After Minimally Invasive Decompression Surgery for Lumbar Spinal Stenosis
Authors: Yamada Kentaro , Toyoda Hiromitsu , Takahashi Shinji , Tamai Koji , Suzuki Akinobu , Hoshino Masatoshi , Terai Hidetomi , Nakamura Hiroaki
Published: October 2021

Study Design.

Retrospective longitudinal cohort study.

Objective.

To investigate the impact of facet joint opening (FJO) on clinical outcomes after minimally invasive decompression surgery for lumbar spinal stenosis.

Summary of Background Data.

Although FJOs have previously been identified as indicators of segmental spinal instability, their impact on clinical outcomes after decompression alone surgery has yet to be investigated.

Methods.

This study included 296 patients from a single institution who underwent minimally invasive surgery for lumbar spinal stenosis and were followed up for ≥5 years. Our analysis focused on identifying FJOs at the index decompression level (d-FJO) and at multiple levels (m-FJO) (i.e., ≥3 levels within the lumbar segment) using preoperative computed tomography. Clinical outcomes including reoperations, improvement ratio for Japanese Orthopaedic Association score, and achievement of a minimal clinically important difference in visual analogue scale scores for low back pain or leg pain at 5 years were compared between patients with and without d-FJO or m-FJO.

Results.

There were 129 (44%) and 62 (21%) patients with d-FJO (more common with lateral olisthesis) and m-FJO (less common with spondylolisthesis), respectively. Reoperations were more common in patients with d-FJO than in those without (16% vs. 5%). On Cox proportional hazards analysis, d-FJO was identified as a predictor for revision at the index decompression level (hazard ratio 4.04, P = 0.03), whereas m-FJO was a predictor for revision at other lumbar levels (hazard ratio 3.71, P = 0.03). Patients with m-FJO had slightly lower rates of achieving minimal clinically important difference in visual analogue scale scores for low back pain (34% vs. 52%, P = 0.03) and poorer improvement ratio for Japanese Orthopaedic Association scores (74% vs. 80%, P = 0.03) than those without.

Conclusion.

FJO at both index decompression level and multiple level were predictors of poor outcomes; patients with FJOs require careful surgical planning or special follow-up.

Level of Evidence: 3
UBE2C affects breast cancer proliferation through the AKT/mTOR signaling pathway
Authors: Lu Zi-Nan , Song Jia , Sun Tong-Hui , Sun Gang
Published: October 2021

Background:

Ubiquitin-conjugating enzyme E2C (UBE2C) has been shown to be associated with the occurrence of various cancers and involved in many tumorigenic processes. This study aimed to investigate the specific molecular mechanism through which UBE2C affects breast cancer (BC) proliferation.

Methods:

BC-related datasets were screened according to filter criteria in the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. Then differentially expressed genes (DEGs) were identified using Venn diagram analysis. By using DEGs, we conducted the following analyses including Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI), and survival analysis, and then validated the function of the hub gene UBE2C using quantitative reverse transcription-polymerase chain reaction (RT-qPCR), cell counting kit-8 (CCK-8) assay, transwell assay, and Western blot assay.

Results:

In total, 151 DEGs were identified from the GEO and TCGA databases. The results of GO analysis demonstrated that the DEGs were significantly enriched with mitotic nuclear division, lipid droplet, and organic acid-binding. KEGG analysis showed that the peroxisome proliferators-activated receptor (PPAR) signaling pathway, regulation of lipolysis in adipocytes, and proximal tubule bicarbonate reclamation were significantly enriched in the signal transduction pathway category. The top three hub genes that resulted from the PPI network were FOXM1, UBE2C, and CDKN3. The results of survival analysis showed a close relationship between UBE2C and BC. The results of CCK-8 and transwell assays suggested that the proliferation and invasion of UBE2C knockdown cells were significantly inhibited (P < 0.050). The results of Western blot assay showed that the level of phosphorylated phosphatase and tensin homology deleted on chromosome 10 (p-PTEN) was obviously increased (P < 0.050), whereas the levels of phosphorylated protein kinase B (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), and hypoxia-inducible factor-1 alpha (HIF-1α) were dramatically decreased (P < 0.050) in the UBE2C knockdown cell.

Conclusion:

UBE2C can promote BC proliferation by activating the AKT/mTOR signaling pathway.
Fenofibrate ameliorates olanzapine’s side effects without altering its central effect: emphasis on FGF-21–adiponectin axis
Authors: Galal Aya , El-Bakly Wesam M. , El-Kilany Sara S. , Ali Azza A. , El-Demerdash Ebtehal
Published: October 2021

The present work was designed to investigate whether fenofibrate could ameliorate olanzapine deleterious effect on insulin resistance via its effect on fibroblast growth factor-21 (FGF-21)–adiponectin axis without affecting olanzapine antipsychotic effect in postweaning socially isolated reared female rats. Treatment with olanzapine (6 mg/kg, intraperitoneally) or fenofibrate (100 mg/kg, orally) have been started 5 weeks after isolation, then behavioral tests, hippocampal content of neurotransmitters, and brain-derived neurotrophic factor (BDNF) were assessed. Moreover, insulin resistance, lipid profile, FGF-21, adiponectin, inflammatory, and oxidative stress markers of adipose tissue were assessed. Treatment of isolated-reared animals with olanzapine, or fenofibrate significantly ameliorated the behavioral and biochemical changes induced by postweaning social isolation. Co-treatment showed additive effects in improving hippocampal BDNF level. Besides, fenofibrate reduced the elevation in weight gain, adiposity index, insulin resistance, lipid profile, and FGF-21 level induced by olanzapine treatment. Also, fenofibrate increased adiponectin level which was reduced upon olanzapine treatment. Moreover, fenofibrate improved both adipose tissue oxidative stress and inflammatory markers elevation as a result of olanzapine treatment. Fenofibrate could ameliorate olanzapine-induced insulin resistance without affecting its central effect in isolated reared rats via its action on FGF-21–adiponectin axis.
Proteomic Biomarker Analysis of Serum from Japanese Field Mice (Apodemus Speciosus) Collected within the Fukushima Difficult-to-return Zone
Authors: Sproull Mary , Hayes Joshua , Ishiniwa Hiroko , Nanba Kenji , Shankavaram Uma , Camphausen Kevin , Johnson Thomas E.
Published: October 2021

The environmental impact of the Fukushima Daiichi nuclear power plant accident is a source of ongoing concern as there is uncertainty regarding the effects of chronic radiation exposure on local plant and animal life from Fukushima-derived radionuclides. In the current study, changes in proteomic biomarker expression due to chronic environmentally-derived radiation exposures was examined in wild field mice. Serum from 10 wild field mice (Apodemus speciosus) native to the Fukushima difficult-to-return zone and from eight wild field mice native to the Soma area (control) were collected. External dose estimations were completed using measurements of ambient radiation levels and calculating 137Cs concentrations in soil. Internal dose was estimated by counting whole mice using an HPGe detector. Age of the mice was estimated using molar wear. Serum was screened using the aptamer-based SOMAscan proteomic assay technology for changes in expression of 1,310 protein analytes. A subset panel of protein biomarkers that demonstrated significant changes in expression between control and exposed mice was determined and analyzed using Ingenuity Pathway Analysis (IPA). Control animals had a calculated lifetime dose range from 0.001 to 0.007 Gy, and exposed animals had a calculated lifetime dose range from 0.01 to 0.64 Gy. No discernable effect of dose rate was seen as relative dose rate correlated with dose for all samples. Detectable values were obtained for all 1,310 proteins included in the SOMAscan assay. Subset panels of proteins demonstrating significant (p < 0.05) changes in expression with either an upregulated or downregulated 1.5-fold change over control were identified for both the sample cohort inclusive of all exposed samples and the sample cohort restricted to samples from animals receiving “low” dose exposures. These panels of proteins from exposed animals were analyzed using IPA, which highlighted changes in key biological pathways related to injury, respiratory, renal, urological, and gastrointestinal disease, and cancer. Significant changes in expression of proteomic biomarkers were seen in the serum of wild field mice that received environmental exposure to Fukushima-derived radionuclides. Our findings demonstrate novel biomarkers of radiation exposure in wildlife within the Fukushima difficult-to-return zone.